Polydopamine and Its Derivative Materials: Synthesis and Promising

Review pubs.acs.org/CR

Polydopamine and Its Derivative Materials: Synthesis and Promising Applications in Energy, Environmental, and Biomedical Fields Yanlan Liu,†,‡ Kelong Ai,† and Lehui Lu*,† †

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People’s Republic of China ‡ Chinese Academy of Sciences, Beijing 100039, People’s Republic of China 6.4. Tooth Remineralization and Tissue Engineering 6.5. Re-endothelialization of Vascular Devices 6.6. In Vivo Cancer Diagnosis and Photothermal Therapy 6.7. Bioimaging 6.8. Drug Delivery 7. Applications in Water Treatment 7.1. Separation of Heavy Metal, Organic Pollutants, and Bacteria from Water 7.2. Water/Oil Separation 7.3. Seawater Desalination 8. Sensing Applications 8.1. Polydopamine as the Grafting Material for Sensing Applications 8.1.1. Detection of Small Organic Molecules 8.1.2. Detection of Biomolecules 8.1.3. Detection of Heavy Metal Ions 8.2. Polydopamine as the Recognition Element for Sensing Applications 8.2.1. Molecular Imprinting Technique-Based Detection 8.2.2. Colorimetric Detection 9. Other Applications 10. Concluding Remarks and Outlook Author Information Corresponding Author Notes Biographies Acknowledgments References Note Added after ASAP Publication

CONTENTS 1. Introduction 2. Preparation and Polymerization Mechanism 3. Physicochemical Properties 3.1. Optical Properties: Absorption and Fluorescence 3.2. Paramagnetism 3.3. Electrical Conductivity 3.4. Adhesive Property 3.5. Metal Ions Chelating and Redox Activities 3.6. Chemical Reactivity 3.7. Biocompatibility and Biodegradation 3.8. Other Properties 4. Polydopamine-Derived Hybrid Materials 4.1. Functional Substrates 4.2. Noble Metal Nanocomposites 4.3. Graphene-Based Nanocomposites 4.4. Metal Oxide−Polydopamine Core/Shell Nanostructures 4.5. Hydrogels 4.6. Hydroxyapatite and Calcium Carbonate 4.7. Synthetic Membranes 4.8. Polydopamine Microfluidic System 4.9. Polydopamine Capsules 4.10. Carbon Materials 5. Applications in Energy 5.1. Batteries 5.1.1. Li-Ion Batteries 5.1.2. Dye-Sensitized Solar Cells 5.2. Supercapacitors 5.3. Catalysts 5.3.1. Electrocatalysts 5.3.2. Photocatalysts and Chemical Catalysts 6. Applications in Biomedical Science 6.1. Cells Adhesion, Encapsulating, and Patterning 6.2. Polydopamine Coating-Induced Toxicity Attenuation of Materials 6.3. Antimicrobial Applications © 2014 American Chemical Society

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1. INTRODUCTION The observation and investigation of phenomena in the natural world can inspire the discovery of new materials and a greater understanding of the underlying physical processes. The development of artificial superhydrophobic materials that mimic the self-cleaning of lotus leaves and the fabrication of periodic microstructures motivated by an examination of the color of butterfly wings are good examples of such discoveries from the fields of materials science and nanostructures.1−3 Research that extends from an examination of fascinating natural phenomena can lead to the development of advanced

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Received: July 27, 2013 Published: February 11, 2014 5057

dx.doi.org/10.1021/cr400407a | Chem. Rev. 2014, 114, 5057−5115

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Figure 1. (A) A brief timeline for the development of polydopamine. Here, we highlight some representatives throughout the history of polydopamine. (B) The number of publications in terms of polydopamine sorted by year. Data were collected from the “Web of Science”. The word “polydopamine” is keyed into the “topic” search box (date of search: 27 September, 2013).

surfaces, with controllable film thickness and durable stability. Thus, polydopamine has opened a new route to the modification of various substrates and has stimulated extensive research. Polydopamine is also a major pigment of naturally occurring melanin (eumelanin).18 Consequently, polydopamine displays many striking properties of naturally occurring melanin in optics, electricity, and magnetics, and, most importantly, it processes excellent biocompatibility. Another valuable feature of polydopamine lies in its chemical structure that incorporates many functional groups such as catechol, amine, and imine. These functional groups can serve as both the starting points for covalent modification with desired molecules and the anchors for the loading of transition metal ions, which can further realize the emergence of diverse hybrid materials by virtue of its powerful reducing capability toward these metal ions under basic conditions. With these benefits, polydopamine is, unsurprisingly, not restricted to use as a coating material and has been rapidly incorporated into a wide range of applications across the chemical, biological, medical, and materials sciences, as well as in applied science engineering, and the technology fields. The fabrication and broad applications of polydopaminebased materials have rapidly advanced in recent years, as indicated by the large number of publications from its advent as a coating material in 2007 to the present day, 2013 (Figure 1). This trend clearly reveals the global significance of polydopamine and the intense interest of scientific research in this field. Note that investigations in the earlier period focused on the functionalization of substrates and the applications of polydopamine in biomedicine; the only three reviews, to the best of our knowledge, gave a brief summary of the polymerization process and some biomedical applications of polydopamine.19−21 Over time, polydopamine-derived materials found new applications in the biological and biomedical fields. Since 2011, polydop-

materials with outstanding properties, which may pave new ways for resolving key issues that long plagued scientist and therefore have quickly developed into a fruitful research field. In modern materials science, surface coatings and their modifications afford protection of the underlying materials from external erosion by agents such as strong oxidants, acid, or base. Furthermore, modification of the surfaces allows control of the surface properties and confers new functionalities to them, a feature that is especially important in some critical fields.4−6 For instance, self-assembly of materials relies largely on the surface energy and the nature of the surface functional groups. Engineering of biosensors or biodevices requires surfaces to be highly biocompatible and rich in functional groups. In general, the currently existing tools for the modification of the surfaces of materials such as chemical conjugation, hydrolysis, layer-by-layer assembly, and plasma treatment are typically time-consuming and complicated processes, and they are not applicable to all surfaces.7−12 Therefore, central to the efforts in this field is a drive to search for an efficient and simple coating approach that is applicable to any surface, a challenge that remains unresolved. The observation of the adhesion of invertebrate mussels to solid surfaces led to an important advance in the field of materials science. Mussels can strongly attach to diverse substrates with high binding strength, even on wet surfaces. Scientists have long investigated the wet adhesion property of mussels. It was found that 3,4-dihydroxy-L-phenylalanine (DOPA) and lysine-enriched proteins near the plaque− substrate interface are the major origins of the extraordinarily robust adhesion.13−16 On the basis of these findings, polydopamine, with a molecular structure similar to that of DOPA, moved into the spotlight as a novel coating material in 2007.17 The primary advantage of polydopamine is that, as seen with mussels, it can be easily deposited on virtually all types of inorganic and organic substrates, including superhydrophobic 5058


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Figure 2. (A) Biosynthetic pathways of eumelanin in organism.18 Reprinted with permission from ref 18. Copyright 2010 American Chemical Society. (B) “Eumelanin” model of the molecular mechanism behind the formation of polydopamine.22 Reprinted with permission from ref 22. Copyright 2011 American Chemical Society.

able dopamine hydrochloride is typically used) are added into an alkaline solution, the polymerization of dopamine monomers immediately occurs, coupled with a color change from colorless to pale brown, and finally turning to deep brown with passing time. To achieve a polydopamine film on substrates, the concentration of dopamine monomer must be higher than 2 mg/mL. The thickness of the polydopamine film can be controlled by tuning the concentration of dopamine monomers and the polymerization time. Nevertheless, the maximum thickness of the resulting polydopamine film in a single reaction step is about 50 nm, a limit that has not yet been accounted for thus far. Further increasing the concentration of the dopamine monomer or prolonging the reaction time does not help to increase the thickness of the film.22 Complementary to this method, it is also possible to produce polydopamine by means of an enzymatic oxidation process. The use of enzymes to catalyze the synthesis of polymer has aroused growing interest, as it is an environmentally benign procedure.23 Indeed, the formation of melanin in organisms is also based on the catalytic oxidation of L-tyrosine by tyrosinase. Laccase is a kind of multi copper-containing polyphenol oxidase and is widely used in industrial processes such as catalytic degradation of phenolic compounds in wastewater. A number of studies in the enzymatic polymerization of phenolic compounds, phenol derivatives, and aromatic amines have been reported in recent years.24−27 The diphenolic structure of dopamine has also been demonstrated to undergo oxidation followed by polymerization into polydopamine by the action of laccase at pH 6.27 As compared to the previously mentioned solution oxidation method, this enzyme-catalyzed method offers the advantage of the entrapment of laccase in the polydopamine matrix with preserved enzymatic activity, and the resulting structure is appealing when thinking of biosensing applications, as we will discuss in section 8.1. Alternatively, electropolymerization of dopamine monomers has also been employed for the direct deposition of polydopamine on electrodes.28 This electropolymerization

amine has undergone significant expansion in its applications and is becoming one of the most attractive areas within the materials field. Despite these advances, there still has been no systematic examination of the polymerization mechanism, properties, and broad applications of polydopamine in different research fields. The aim of this Review, therefore, is to deliver a comprehensive overview of the relevant advances in the field of polydopamine since its advent as a smart coating material in 2007. At the beginning of the first section, we will shortly introduce the synthesis approaches of polydopamine. We will then dedicate a lot of space in this section to discuss the polymerization mechanism as well as the factors that influence this polymerization process. Several models that have been proposed so far will be described in this section. This Review will also include an overview of the physical properties of polydopamine in terms of optics, electricity, and magnetics, as well as its chemical reactions and other potential properties. Following this section, we will present some representative polydopamine-derived functional materials in light of these physicochemical properties of polydopamine, with a focus on the diverse applications of these materials including in energy, environment, and sensing disciplines, as well as the biological and biomedical fields. A straightforward summary of this Review and some key issues that exist in this emerging field and must be taken into consideration in the future research will be given in the last section as well.

2. PREPARATION AND POLYMERIZATION MECHANISM The solution oxidation method is the most widely used protocol for the production of polydopamine. Its monomer, dopamine, can be oxidized and spontaneously self-polymerize under alkaline conditions (pH > 7.5) with oxygen as the oxidant. This self-polymerization reaction is so mild without the need for any complicated instrumentation or harsh reaction conditions. When dopamine monomers (commercially avail5059


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Figure 3. Proposed formation and structure of polydopamine. In this model, polydopamine is proposed to be comprised of intra- and interchain noncovalent interactions including hydrogen bonding, π-stacking, and charge transfer.41 Reprinted with permission from ref 41. Copyright 2012 American Chemical Society.

In marked contrast to the “eumelanin” model, which envisages a polymeric skeleton based on the covalent bonds between the aryl rings of the monomers, very recently, Bielawski and co-workers utilized solid-state spectroscopic and crystallographic techniques to propose a new structural model for polydopamine.41 Using solid-state 15N nuclear magnetic resonance (NMR) data, the authors confirmed the formation of cyclized, nitrogenous species such as the indole- or indoline-type structures, consistent with the above models. However, on the basis of the one-dimensional solid-state 13C NMR analysis, the cyclized, nitrogenous species were ascribed to a saturated indoline structure, rather than an unsaturated indole structure in the aforementioned models. Furthermore, polydopamine was considered to be an aggregate of monomers, which were cross-linked primarily via strong, noncovalent forces, including hydrogen bonding, charge transfer, and πstacking, similar to other synthetic or biological supramolecular polymers (Figure 3). In parallel with these two models, Lee and co-workers suggested that the formation of polydopamine was a result of the combination of noncovalent self-assembly and covalent polymerization.42 Derived from high-performance liquid chromatography (HPLC) coupled with mass spectrometry analysis, these investigators identified a considerable amount of dopamine that remained unpolymerized and that formed a selfassembled complex with its oxidative product, 5,6-dihydroxyindole (DHI), as depicted in Figure 4. Further HPLC analysis verified that the encapsulation of dopamine was quite stable with a very low amount being released from the matrix. Simultaneously, the previously proposed pathway of covalent bond-forming oxidative polymerization also occurred. The resultant (dopamine)2/DHI physical trimers were tightly entrapped within the oxidative polymerization product, leading to the formation of a brown-black polydopamine precipitate, which might be due to the intermolecular interactions involving H-bonding, T-shape interaction, and cation−π interaction. Another proposal advanced by Vecchia and colleagues integrates and expands new concepts of the structure of polydopamine presented in the aforementioned models.43 These authors suggested that the formation of polydopamine would undergo three main competing pathways (Figure 5) and

process can proceed in deoxygenated solution with cyclic voltammetry within a given potential range and with a potential-sweep rate. With this protocol, polydopamine can be directly deposited on the electrode with a greater film thickness as compared to the solution oxidation method under the same concentration of the monomer. Despite simplicity and effectiveness, there are still some inherent limitations in the electropolymerization fabrication method with the main one being that only electrically conductive materials support the surface electropolymerization. Although polydopamine can be produced in a facile and simple polymerization process, the molecular mechanism behind the formation of polydopamine has long been the topic of scientific debate, which continues to this day, due to the complex redox process as well as the generation of a series of intermediates during the polymerization and reaction processes. In the early stages of this research field, the formation of polydopamine was believed to follow a process similar to the synthetic pathway of the melanin (eumelanin) in living organism.29−39 As illustrated in Figure 2B, under alkaline conditions, dopamine is first oxidized to dopamine-quinone followed by intramolecular cyclization via 1,4 Michael-type addition to yield leucodopaminechrome.40 Thereafter, leucodopaminechrome further suffers from oxidization and rearrangement to form 5,6-dihydroxyindole, which is easily oxidized to 5,6-indolequinone. These two reaction products are capable of undergoing branching reactions at positions 2, 3, 4, and 7, leading to the formation of multiple isomers of dimers and, eventually, higher oligomers, which self-assemble through the reverse dismutation reaction between catechol and o-quinone to give the cross-linked polymer. However, little solid experimental evidence has been found for this “eumelanin” model. Preliminary verification of this polymerization mechanism was obtained only by FTIR analysis.30 The disappearance of the peaks at 1519 cm−1 (NH2 scissoring vibration) and 1342 cm−1 (CH2 bending vibration), the relatively large absorbance in the 1500−1100 cm−1 region, as well as the broadened width of the peak at 1630 cm−1 in the FTIR spectrum of the polymer as compared to that of dopamine monomer all verified the intramolecular cyclization reaction had occurred in dopamine along with the formation of indole derivatives. 5060


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Figure 4. Two reaction pathways for the formation of polydopamine: (A) covalent bond forming oxidative polymerization, and (B) a newly proposed pathway of physical self-assembly of dopamine and DHI.42 Reprinted with permission from ref 42. Copyright 2012 Wiley-VCH.

NMR spectra of the polydopamine samples identified the incorporation of Tris into the polydopamine structure; this incorporation was found to be significant during the polymerization process at relatively low concentrations of the monomer. The pathways illustrated in Figure 5 reflect that covalent-bond interaction plays a critical role during the initial steps of polydopamine buildup, while noncovalent bond interactions may play a greater role after the oligomerization reaction has proceeded significantly. Another major implication of Figure 5 is that many functional groups including planar indole units, amino group, carboxylic acid group, catechol or quinone functions, and indolic/catecholic π-systems are integrated into polydopamine, which may specifically explain the robust adhesion capability of polydopamine to virtually all types of surfaces, and also provides a versatile platform for further loading of conjugates with other interesting functionalities. In addition to the concentration of dopamine and the type of the buffer used, attention also needs to be paid to the effect of the pH value of the reaction solution on the polymerization

the structure of polydopamine would change depending on the preparation conditions, such as the concentration of starting dopamine and the category of buffers. The data including 13C NMR, 15N NMR, and UV−visible spectra varied significantly from sample to sample. For instance, at a very low concentration of starting dopamine (0.5 mM), the quinone was generated slowly, and it was less likely to be trapped by dopamine, leading to a higher proportion of cyclized indole (DHI) units. Moreover, the intense resonances around δ = 170 ppm in the 13C NMR spectra of the resultant polydopamine suggested the presence of a proportional level of pyrrolecarboxylic acid fragments via oxidative fission of catechol moieties in the DHI units, due to the generation of hydrogen peroxide during this process. At a higher concentration of starting dopamine (10 mM), nevertheless, the quinone generated by autoxidation might be efficiently trapped by dopamine, resulting in an increased amount of uncyclized elements as illustrated by 13C NMR and 15N NMR analysis. Besides, when tris(hydroxymethyl)-aminomethane (Tris) buffer was used instead of phosphate and NaHCO3 buffers, 13C solid-state 5061


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Figure 5. Schematic illustration of possible reaction routes involved in the formation of polydopamine. This model suggests that both covalent and noncovalent bond interactions occur and play different roles in the formation of polydopamine.43 Reprinted with permission from ref 43. Copyright 2013 Wiley-VCH.

process.44 When the pH value of the solution increased from 5 to 8.5, the thickness of the deposited polydopamine film gradually increased and leveled off at pH values higher than 8.5. This is not hard to understand according to the equilibrium as depicted in Figure 6. As the pH increases, the oxidationproduced hydrogen protons will be consumed, and the equilibrium will shift toward the product. The use of the oxidant in the reaction solution is another crucial factor for the formation of polydopamine. As illustrated above, oxygen is frequently used as the oxidant during the polymerization process. Oxygen participates in the initial oxidation of dopamine as well as converting 5,6-dihydroxyindole into the corresponding quinone via hydrogen abstraction. Thus, dopamine will not polymerize in solutions that have been deoxygenated under vacuum and without the presence of other oxidants, in principle, even at a strongly alkaline environment. This hypothesis has been confirmed in a recent study where the addition of NaOH into a dopamine aqueous solution did not lead to any color change of the solution under permanent bubbling of nitrogen gas.45 Some oxidants other than oxygen such as ammonium persulfate, sodium periodate, sodium perchlorate, and metal ions are also proved to be effective in the polymerization of dopamine.22,26,29,46−50 An interesting, but as yet unexplained phenomenon is that with ammonium persulfate and copper

Figure 6. First steps of the formation of polydopamine.22 Reprinted with permission from ref 22. Copyright 2011 American Chemical Society.

ions as oxidants, the deposition of polydopamine typically occurred even under acidic conditions (pH 4), and the thickness of the deposited polydopamine film was even larger than that obtained when using oxygen as the oxidant with other conditions unchanged.22 At first glance, this outcome appears to be paradoxical with respect to the above description, because the equilibrium illustrated in Figure 6 would shift toward the 5062


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a similar photoprotection effect. Nevertheless, the direct use of polydopamine as a photoprotective agent has yet to be systematically investigated. There also has long been a controversy with respect to the fluorescence of eumelanin. One may not dispute when reading or hearing the phrase “eumelanin does not fluoresce”, but this is not the case. Upon excitation by UV or visible light, both the synthetic and the naturally occurring eumelanins have been validated to emit radiatively.58,59 Nevertheless, their radiative quantum yields are extremely low (about 0.2% for dopaminemelanin), as the majority of absorbed energy is subjected to nonradiative dissipation as discussed above.60−63 This in turn explains why melanin has commonly been considered to be nonfluorescent in the earlier literature. The same applies to polydopamine. Under excitation with UV light, polydopamine exhibits a weak fluorescence with peak emission at 400−550 nm, and the emission is dependent on the excitation wavelength. This phenomenon seems to be at odds with that of common organic fluorescent substances, and further indicates its inherent chemical heterogeneity. The chemical disorder model may be suitable for the interpretation of the optical features that are observed in spectroscopic studies of eumelanin, as well as polydopamine.64 Similar to naturally occurring eumelanin, polydopamine contains both DHI and DHICA units as shown in section 1. The oxidation of both DHI and DHICA, as well as oligomerization and stacking of oligomers, lead to the formation of a range of chemically distinct species that possess a series of highest occupied molecular orbital (HOMO)− lowest unoccupied molecular orbital (LUMO) gaps in the UV, visible, and near-IR regions, resulting in the observed monotonic, broadband absorbance. Likewise, excitation-dependent emission can also be explained by this model. Different components within the ensemble have differential excitation energies and quantum yields.

reactant under acidic conditions. Unfortunately, the details of the reaction mechanism are still not well understood. It has been speculated that copper ions are most likely to serve as a glue to allow for the agglomeration of small oligomers. Here, it should also be pointed out that, besides oxidants, proper elevation of the reaction temperature can also accelerate the deposition of polydopamine.

3. PHYSICOCHEMICAL PROPERTIES On a simple level, polydopamine has long been considered as a polymer coating material inspired by nature. During the past few years, research on polydopamine has therefore been directed toward the construction of smart polydopaminecoated functional substrates based on the inherent adhesive property of polydopamine. However, the function of polydopamine is not limited to adhesion. Thus, well understanding the fundamental properties of polydopamine in depth may promote more exchanges of ideas from various research fields to accelerate diversifying, extending, and unleashing potential applications toward polydopamine in the future. Because polydopamine shares common features with naturally occurring eumelanin in terms of the chemical component and structure, the physical properties of polydopamine therefore largely overlap with those of naturally occurring eumelanin. In this section, we will summarize the explored properties of polydopamine, while acknowledging that all of the properties of polydopamine have not been fully defined. 3.1. Optical Properties: Absorption and Fluorescence

Naturally occurring eumelanin is well-known to have broadband monotonic absorption ranging from the ultraviolet to the visible region.51 Various investigators have offered different views to explain the origin of the broad absorption spectrum of eumelanin, but the topic remains under discussion. Initially, the broadband absorption spectrum was thought to arise from light scattering rather than from electronic or physical properties of the eumelanin itself.52−54 However, the detected optical scattering coefficients in those studies differed from one another. In 2006, Riesz et al. performed a detailed study and proved that the scattering contributed less than 6% to the total optical attenuation between 210 and 325 nm, and the scattering was found to be less than the minimum sensitivity of the instrument at the wavelength ranging from 325 to 800 nm.55 These results implied that the optical density spectrum of eumelanin across all wavelengths can be interpreted as true absorption. Other authors have further illustrated that more than 99% of the absorbed photon energy will be converted nonradiatively into heat within 50 ps.56 Such a broad absorption and high photothermal conversion ability protect humans and animals from ultraviolet injury. Polydopamine, as the major pigment of eumelanin, typically shows an absorption property similar to that of the naturally occurring eumelanin: the absorption increases exponentially toward the ultraviolet spectrum. Because there is no distinct chromophoric band, scientists are prone to believe that polydopamine is a disordered organic semiconductor, similar to melanin. The appearance of the absorption in the UV region of the light spectrum was ascribed to the oxidation of dopamine into dopachrome and dopaindole, and a pronounced absorption extending from visible to NIR wavelengths is considered to be the result of the subsequent self-polymerization process.48,57 Because of its strong absorbance in the ultraviolet wavelengths, polydopamine is also expected to show

3.2. Paramagnetism

Paramagnetism is one of the most unusual features of naturally occurring melanin over other biopolymers, because of the presence of stable π-electron free radical species, which can induce a persistent electron spin resonance (ESR) signal.65−68 Eumelanin-like polydopamine also displays a single-line ESR spectrum similar to that of the naturally occurring eumelanin, and a single peak was observed with a g-factor approaching 2. This finding suggests the presence of an irregular, cross-linked polymer network with mixed bonding arrangements and radicals localized to single quinone residues.69 The widely accepted equilibrium between the different redox states of melanin monomer units is as follows: QH 2 + Q → 2Q· + 2H+

(1)

where QH2, Q, and Q· represent the quinol units, quinone units, and free radicals, respectively. According to this equilibrium, the concentration of melanin free radicals will vary when melanin interacts with reducing agents, oxidization agents, or some metal ions.70−72 For instance, Zn2+ ions have been confirmed to be capable of increasing the free radical signal of melanin-like polydopamine nanoparticles, which is known to be a key feature of naturally occurring melanin. However, coordination with some paramagnetic metal ions such Cu2+, Mn2+, or Fe3+ can dramatically reduce the observable ESR signal. 5063


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This distinct free radical character allows melanin to act as a radical trap in the biological systems. Its interesting abilities to scavenge reactive free radicals, quench electronically excited dye molecules, and sequester redox active metal ions have conferred to melanin strong antioxidant effects in the organism. The radical scavenging ability of polydopamine has also been evaluated in vitro based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay.45 At a dose level of 120 μg, polydopamine nanoparticles could scavenge 85% of DPPH organic free radicals, as monitored by the decrease in the absorbance and the ESR signal of DPPH. More interestingly, the radical scavenging activity of polydopamine nanoparticles had a trend of increasing as the nanoparticle size decreased, being comparable to the value of ascorbic acid, a well-known free radical scavenging material. Ju et al. reasoned that the decrease of the particle size led to an increase of the surface-to-volume ratio, coupled with more available reaction sites exposed on the surface of the polydopamine nanoparticles. These results clearly revealed the great promise of polydopamine-based materials as therapeutic antioxidants. Nevertheless, the in vivo therapeutic antioxidant effect of polydopamine-based materials has yet to be investigated until now, possibly accounting for the lack of full details of their in vivo toxicity, even though they behave as a pigment of naturally occurring melanin.

cosubstrates during the polymerization process and can allow fine-tuning of its electronic properties. 3.4. Adhesive Property

One of the most important properties of polydopamine that particularly intrigues physicists and chemists is its robust and strong adhesion to virtually all types of surfaces, regardless of the substrate’s chemistry. Although there is a general acceptance that the catechol group plays the central role in such mussel-mimicking versatility,78−82 the exact adhesion mechanism remains elusive. Fully understanding how polydopamine diffuses on different substrates can give insights into the assembly processes and guide the design of hybrid materials, but has proved to be challenging. Overall, the interactions of polydopamine with substrates that merge from previous findings are varied depending on the surface properties of the substrates and may be divided into two types: covalent binding and noncovalent binding. It is easy to imagine that a covalent binding mechanism is applicable to some specific substrates that contain amine and/ or thiol groups on their surfaces via Michael addition and/or Schiff base reactions under basic conditions. Under ambient conditions, on the other hand, polydopamine, similar to its monomer, is prone to diffusion on substrates through noncovalent binding interaction such as metal coordination or chelating, hydrogen bonding, π−π stacking, and quinhydrone charge-transfer complexes to yield an effective adlayer.83−96 Metal ions can chelate with catechol groups in polydopamine, and metal or metal oxide surfaces are usually hydroxylated or hydrated under ambient conditions. As a result, coordination bonding and chelating bonding interactions play central roles in the adhesion of polydopamine on metal or metal oxide surfaces. For instance, Fe2O3, Al2O3, ZrO2, etc., have been reported to be coated with polydopamine via the coordination interaction between metal and the catechol group. In some cases, several interactions may be involved between polydopamine and substrates. A characteristic example is the interaction of catechol with the TiO2 surface, but the binding between these two entities remains a controversial subject. For example, a plausible explanation for catechol to chemisorb on the TiO2 surface was reported via the coordination between catechol and one Ti atom.91 Definitely different from this explanation, Rajh et al. proposed that catechol was anchored on the TiO2 surface through bidentate chelating bonding.92 Similarly, on the basis of the fact that the TiO2 surface is composed of 5-fold-coordinated Ti atoms separated by rows of 2-fold-coordinated, bridge-bonded O atoms, Messersmith and colleagues as well as other groups also proposed that catechol reacted with two hydroxyl groups on the TiO2, leading to bridged bidentate bonding.93,94 Sticking to organic and hydrophobic surfaces is a most striking advantage of polydopamine as compared to previous coating materials. However, the detailed binding mechanism is still not well-known. By the aid of atomic force microscopy (AFM), Lee et al. demonstrated that the mechanism behind polydopamine adhesion to organic surfaces relied on the oxidation of the catechol to quinones occurring in the alkaline environment, leading to covalent coupling to organic surfaces via aryl−aryl coupling or possibly via Michael-type addition reactions.86 Despite the incomplete understanding of the binding mechanisms, scientific research regarding polydopamine has not been hindered, and the robust adhesion of

3.3. Electrical Conductivity

Since the discovery of reversible electrical switching properties of eumelanin in the 1970s, melanin, in particular eumelanin, has been widely suggested to be a naturally occurring amorphous organic semiconductor.73,74 In this model, the HOMO and LUMO levels of eumelanin correspond to the valence band and conduction band in semiconductors, respectively. Eumelanin is composed of aromatics and conjugated molecules. As a result, both HOMO and LUMO levels in eumelanin are characterized by the π-system. The movement of charge carriers through the π-systems would lead to conductivity and semiconducting properties in eumelanin. The electrical conductivity of eumelanin, both synthetic and naturally occurring, was observed to be strongly dependent on the temperature, physical form, and the humidity of the measurement conditions.75,76 For instance, the changes in the humidity of the measurement conditions would change the local dielectric constant as water is absorbed into eumelanin. A synthetic dopamine-melanin showed conductivity as low as 10−13 S/m in vacuum, while the conductivity increased to as much as 10−5 S/ m at 100% relative humidity due to the full hydration.75 In contrast, Meredith and co-workers recently described eumelanin as an electronic−ionic hybrid conductor rather than an amorphous organic semiconductor based on the electrical conductivity, muon spin relaxation, and electron paramagnetic resonance measurements.77 These authors have demonstrated that upon the absorption of water, free carriers would be produced according to the comproportionation reaction with the accompanying production of extrinsic free radicals (electrons) and hydronium ions (protons), giving rise to hybrid ionic−electronic behaviors. Given their good biocompatibility, understanding the electrical properties of melanin opens a new way for the fabrication of bioelectronic devices based on melanin-like materials. A key point to note concerning the difference between polydopamine and naturally occurring melanin is that polydopamine can provide a versatile platform amenable to π-electron manipulation with suitable 5064


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Figure 7. There typical chemical reactions of polydopamine.101,102,155 Reprinted with permission from refs 101, 102, and 155. Copyright 2010 and 2013 American Chemical Society.

groups and a small decrease of catechol groups on the surface of polydopamine film.100 These findings suggested that polydopamine contained a certain amount of catechol groups, and the catechol group was able to release electrons when oxidized into the corresponding quinone group and trigger reduction processes of metallic cations. It is also important to keep in mind that during the formation process of polydopamine, the oxidization of dopamine into dopamine-quinone will release two electrons as described in Figure 6, which can also reduce metallic salts into their corresponding metals, and the subsequent self-polymerization leads to the deposition of polydopamine films on the surfaces of the resultant metals. Such metal ion chelating and redox activity of polydopamine have stimulated considerable interest in the fabrication of diverse organic−inorganic hybrid materials for many practical applications, which will be addressed below.

polydopamine has led to a surge of interest in preparing functional substrates or hybrid materials as we will discuss later. 3.5. Metal Ions Chelating and Redox Activities

The binding of polydopamine to various multivalent metal ions such as Fe3+, Mn2+, Zn2+, and Cu2+, etc., is another most attractive feature. The metal ion bonding is related to many functional groups in polydopamine including o-quinone, carboxy, amino, imine, and phenol groups.97 It is worth noting that different binding sites of polydopamine will be activated at different pH conditions. For example, the binding sites for Cu2+ ions in both synthetic and naturally occurring eumelanins have been determined by ESR spectroscopy using63Cu2+ as the probe.98,99 The results indicated that: (i) At pH values below 5, the ESR spectrum indicated that Cu2+ ions formed a complex with carboxyl groups and bidentate nitrogen-carboxyl groups.

3.6. Chemical Reactivity

(ii) At pH ≈ 7, binding of Cu2+ ions at phenolic hydroxyl groups was detected. (iii) As pH increased further, binding of Cu2+ ions occurred with either three or four nitrogen ligands. Apart from metal ion chelation, polydopamine can also reduce some noble metal ions such as Au3+, Ag+, and Pt3+ under basic environments. The ability of polydopamine to behaving as a reducing agent is, to a large extent, related to the redox character of its monomer units. With the aid of ESR, Ball and co-workers found that the ESR signal of polydopamine film was hardly affected by the deposition of silver nanoparticles, and XPS results showed a small increase in the density of quinone

The many functional groups found in polydopamine are able to react with a wide range of molecules. The most widely investigated reactions in previous literature are the cross-linking reaction of polydopamine with the amine and/or thiolcontaining molecules. The reaction mechanisms are illustrated in Figure 7. The latent reactivity of polydopamine with aminecontaining molecules is a function of catechol/quinone chemical equilibrium in the polydopamine matrix and the pKa of the amine group. Under basic conditions, the catechol in the polydopamine matrix can be oxidized into the corresponding quinone, which can then react with the nucleophilic amine groups by means of a Schiff base reaction. Alternatively, this 5065


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environment within the whole organism. In whole animals, the median lethal dose (LD50) was determined to evaluate the acute toxicity of these reagents. Polydopamine nanoparticles showed a relatively high LD50 (intravenous injection) value of 483.95 mg/kg with a 95% confidence interval of 400.22− 585.19 mg/kg, which suggested their low acute toxicity. The in vivo toxicology of polydopamine nanoparticles has also been preliminarily assessed by monitoring different parameters within a period of 1 month after intravenous administration. All of the treated animals remained healthy without any abnormalities in eating, drinking, grooming, activity, exploratory behavior, urination, or neurological status. The body weight of the polydopamine-treated group gradually increased in a manner comparable to that of the control group. Serum levels of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total protein (TP), and albumin/globin ratio (A/G) are frequently used as critical biochemical indicators of the liver function. Single dose injection of polydopamine nanoparticles did not result in obvious elevation or decrease for any of these indicators, indicating that hepatic function of the mice was normal. On the other hand, complete blood panel test depicted that all of the indicators fell within normal ranges, which revealed no detectable interference with the physiological regulation of heme or immune response. The histopathological examination of several organs including liver, heart, spleen, kidney, and lung revealed a normal parenchymal architecture without any tissue damage, inflammatory, or fibrosis aspect with no detectable change in the cellular structures following the administration of polydopamine nanoparticles.104 Biodegradation in a timely fashion is also required for materials that will be applied to biomedical applications, because long-term retention of foreign substances in the body may trigger serious adverse effects. Melanin would undergo degradation in vitro in the presence of oxidizing agents. For example, the degradation of melanin by the hydrogen peroxide has been thoroughly studied, leading to the formation of pyrrole-2,3-dicarboxylic acid (PTCA) and pyrrole-2,3-dicarboxylic acid (PDCA).107 Such a phenomenon has also been observed with polydopamine nanoparticles. After incubation with hydrogen peroxide, polydopamine nanoparticles lost a significant part of their absorption accompanied by color fading, which suggested the degradation of polydopamine nanoparticles.104 In vivo studies performed by Langer’s group have also demonstrated that polydopamine implants were almost fully degraded after 8 weeks (Figure 8).108 These findings clearly implied that polydopamine can be degraded in vivo. However, the detailed in vivo degradation of polydopamine materials remains unclear thus far, and has not received systematical investigation. A possible pathway for polydopamine biodegradation is the oxidation-induced degradation process, because many active oxygen species such as H2O2 and free radical are generated in the human body, and a major source of these biologically generated active oxygen species is a family of multisubunit enzymes known as nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases), which are widely distributed in phagocytes and in many organs, such as kidney, lung, intestine, and spleen.109 Besides potential enzymatic degradation, polydopamine has also been observed to be degraded by microorganisms. After being immersed in the unsterilized soil, the decomposition rate of polydopamine was found to be faster than that in the sterilized soil as assessed by the release of nitrogen from

cross-linking reaction can proceed via a Michael-type addition pathway. In the case of thiol-containing molecules, these nucleophiles are most likely to react with polydopamine through Michael addition reaction as depicted in Figure 7A. The reactions toward either amine- or thiol-containing molecules are facile, without the need for any harsh reaction conditions or complicated equipment. Simple mixing of these agents at room temperature under basic conditions affords the functionalization of polydopamine. More importantly, couplings with these nucleophiles typically proceed in aqueous environments and remain quite stable, in marked contrast to Nhydroxysuccinimide (NHS) or maleimide agent commonly used as coupling agents between substrate surfaces and amineor thiol-containing molecules, which are susceptible to hydrolysis and thereby result in poor conjugation efficiency. The presence of free amine and imine groups in the polydopamine matrix as illustrated in section 2 permits other types of organic molecules to be attached to the polydopamine under certain conditions. For instance, it has been demonstrated that 1,3,5-benzenetricarbonyl trichloride could react with the free amine groups of polydopamine in an organic solvent (Figure 7C).101 At the high temperature of 150 °C and under vacuum, on the other hand, the cross-linking between imine groups in polydopamine and carboxyl groups in poly(acrylic acid) could take place (Figure 7B).102 These reactions of polydopamine are of great significance because they pave a new and versatile way to the modification of diverse substrates with specific functionalities, and provide an important platform for the construction of hybrid materials. 3.7. Biocompatibility and Biodegradation

Biocompatibility is a vital factor in determining the suitability of a material for specific applications in the biomedical field, especially in experimental small animals and, ultimately, in clinical applications. As a major component of naturally occurring melanin that is widely distributed in the human body, polydopamine is anticipated to show excellent biocompatibility and can significantly decrease the occurrence of serious adverse effects caused by the administration of foreign substances. Determination of the possible toxicity of polydopamine was initially carried out in vitro using the well-known (3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as also assessed for other materials. Studies performed by Ku et al. have demonstrated that polydopamine did not hinder the viability or proliferation of many kinds of mammalian cells such as fibroblasts, osteoblasts, neurons, and endothelial cells.103 In line with these results, a recent investigation showed that polydopamine nanoparticles did not induce obvious cytotoxic effects when in contact with both the mouse 4T1 breast cancer cells and the human cervical cancer cells (HeLa cells), even at very high doses. 104 More interestingly, a lot of investigations have illustrated that polydopamine-coating even promoted cell adhesion and proliferation on substrates in a material-independent manner as compared to the pristine substrates, which further provided strong evidence for the negligible cytotoxicity of polydopamine.105,106 Although in vitro tests can provide valuable information with respect to the cytotoxicity, cell uptake, intracellular distribution, and possible interactions with cells of polydopamine, one must keep in mind that the investigations with isolated cells are far from sufficient and must be completed with in vivo studies, when taking into consideration the complexity of the 5066


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effects such as collapse of the material’s backbone after thermal treatment or erosion or exfoliation of the active species from the electrode’s surface after contact with the electrolyte will occur and diminish the material’s performance. Organic polymers used as coating materials are known to often undergo swelling, dissolution, or hydrolysis after contact with a physiological buffer.114 In contrast, polydopamine exhibited high resistance against these conditions. For example, polydopamine films on silica remained stable in a physiological buffer for at least 4 days. Even at pH 1, only 14% of the film was eroded within 54 h. Such high stability was also observed when polydopamine was deposited on other substrates,115 swelling only slightly when being subjected to PBS for 30 days. In the case of thermal behavior, polydopamine can endure temperatures up to at least 200 °C without suffering any significant decomposition. In addition to these properties as mentioned above, polydopamine has demonstrated other potential functions such as superparamagnism and absorption of ultrasonic sound waves (1 MHz).20

Figure 8. In vivo degradation of polydopamine (synthetic melanin); small fragments of polydopamine implant are visible after 8 weeks (B and D). Scale bars represent 200 mm for low magnification images and 20 mm for high magnification inset images.108 Reprinted with permission from ref 108. Copyright 2009 Elsevier.

4. POLYDOPAMINE-DERIVED HYBRID MATERIALS In light of these physicochemical properties, diverse polydopamine-derived hybrid materials have been fabricated to date, and the functional roles of polydopamine in their formation may be broadly divided into the following four categories: (i) Either as part of a system or by itself, polydopamine serves as the passive link to the surfaces of the materials for improving some critical performance of the initial materials, and/or for facilitating the covalent conjugation with moieties that possess other interesting functionalities. (ii) Polydopamine can behave as both the reducing agent and the stabilization agent for the construction of inorganic−organic hybrid materials. (iii) Polydopamine is, under certain conditions, capable of constituting specific structures, which are functional on their own. (iv) Polydopamine can act as a green carbon resource. Below, we attempt to summarize several types of polydopamine-derived materials according to these functional roles. Only some characteristic examples are highlighted in this part. Additional examples will be presented in the applications sections.

polydopamine. Notably, the decomposition of polydopamine also occurred by microbes in the sterilized soil.110 Admittedly, these investigations performed to date are quite preliminary for an agent that is intended to be used in clinical applications. Some key issues have not been well illustrated, and more-in-depth investigations regarding the long-term toxicity as well as detailed mechanisms and precise mode of in vivo degradation for polydopamine remain as critical needs. Of course, the particle size, surface property, and colloidal stability of polydopamine-based materials should also be taken into account in toxicological assays. 3.8. Other Properties

Because of the presence of many functional groups such as carboxy, amino, imine, and phenol groups, polydopamine can be dispersed in various solvents and displays high hydrophilicity. When both hydrophilic and hydrophobic substrates are coated with polydopamine, the surface energy of both types of substrates will be drastically changed.111 For example, the polar component of the surface energy of L-poly-(lactic-acid) (PLLA) increased from 9.6 to 42.6 mJ/m2 at 24 h after treatment with dopamine Tris buffer (pH 8.5), revealing the polar and hydrophilic characters of polydopamine. The extent of the water contact angle could be decreased by over 50° after 48 h of polymerization.112 In general, the water contact angle of substrates after polydopamine coating falls within a range of 37−90° depending on the nature of substrates. For some special substrates, the value can be lowered to below 20°. The presence of diverse functional groups, on the other hand, further makes polydopamine a zwitterion.113 Its isoelectric point is determined to be around 4. At a pH value below 4, the amino groups in the polydopamine framework will be protonated, leading to a positively charge surface of the polydopamine, whereas at pH values above the isoelectric point, polydopamine will be negatively charged because of the deprotonation of the phenolic groups. For applications in electrochemical sensing and energy, materials with high chemical or thermal stability are highly desirable. If the thermal or chemical stability is poor, adverse

4.1. Functional Substrates

Fine control over the surface properties of substrates plays a vital role in various fields, especially in biotechnology. Currently, approaches under primary investigation for surface modification appear to be case-by-case with no general roles to follow, and rely largely on the relationship between the properties of the substrate and the desired tethering molecules. Developing a facile and versatile surface functionalization protocol toward multiple classes of substrates without the aid of complex instruments, limitations of the nature of the substrate, and the need of multistep procedures will have a profound impact on modern chemical, biological, and material sciences. In 2007, Messersmith and co-workers attempted to simulate the strong adhesion features demonstrated by the foot of the gecko, a lizard that can scale vertical walls with ease. They fabricated a hybrid biologically adhesive that consisted of an array of nanofabricated polymer pillars, which were coated with a thin layer of another polymer containing dopamine units.116 5067


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Figure 9. (A−D) Photograph of mussel and amino acid sequence of Mefp-5 in the foot protein. (F) Schematic illustration of deposition process of polydopamine thin film. (G) The thickness of polydopamine film with increasing deposition time. (H) Electroless metallization of polydopaminecoated substrates. (I) XPS analysis of characteristic substrate signal for 25 different substrates before and after polydopamine deposition.17 Reprinted with permission from ref 17. Copyright 2007 Science.

multifunctional substrates with specific properties. Up to date, grafting of diverse species including DNA,117 proteins,118 growth factors,119−121 PEG,122 polysaccharides,17 hydroxyapatites,197 noble metal nanoparticles,143 graphene oxide,124 polymers,125 enzymes,126 functional living cells,127 and other molecules128−136 onto polydopamine coatings has been accomplished in light of the chemistry reactions, chelating, and reducing abilities of polydopamine coating in the secondary reaction step, giving rise to bioresistant, biointeractive, and/or chemically reactive surfaces. Considering that the postsynthetic modification of polydopamine has been limited to molecules containing either amine or thiol groups, Lee and co-workers have further invested efforts in extending and diversifying this strategy, aiming to make it applicable not only to diverse substrates but also to different chemical functionalities.137 In their study, they first codissolved molecules with dopamine, and then immobilized this mixture on the substrates under a basic environment to yield target molecule-entrapped polydopamine coating. Such an improved method showed a similar effectiveness in modifying versatile surfaces. More specifically, molecules with a wide range in sizes (102−106 Da) and with various chemistries presenting amine,

It was found that the adhesion of polymer pillars increased nearly 15-fold after coating them with the dopamine unitcontaining polymer, and the system could maintain its strong adhesion even after 1000 contact cycles in both dry and wet environments. Thereafter, these authors noted that besides polymer pillars, dopamine could self-polymerize and deposit polydopamine on virtually all types of inorganic and organic surfaces, similar to the case of the adhesion of mussels.17 Only a simple immersion of substrates in an aqueous dopamine solution, which was buffered to pH 8.5, could lead to spontaneous deposition of a polydopamine film with a maximum thickness of 50 nm after 24 h. Excitingly, this method had no limit with respect to the nature of the substrates including factors such as composition, size, shape, and surface properties. As illustrated in Figure 9, various substrates including noble metals, metals with native oxide surface, semiconductors, oxides, ceramics, and synthetic polymers could be successfully functionalized with polydopamine. With the publication of this paper, this straightforward and versatile coating strategy has immediately attracted explosive attention worldwide and opened the possibility to use polydopaminemediated chemistry as a generic way to fabricate numerous 5068


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Figure 10. (A) Surface property changes of cherry tomato and Teflon film after polydopamine coating. (B) Schematic illustration of polydopamineassisted block copolymer lithography for low surface energy substrates. (C) Schematic procedure for the fabrication of Teflon nanowires via polydopamine-assisted block copolymer lithography and typical SEM image of the resultant Teflon nanowires. (D) Schematic illustration of the synthesis, photography, and SEM images of the hierarchically organized vertical CNT array directly grown on an Au substrate.138 Reprinted with permission from ref 138. Copyright 2011 Wiley-VCH.

polydopamine film, and these polydopamine-treated materials could be stably wetted by water (Figure 10A). With the polydopamine coating, hydroxyl-terminated polymer could attach strongly on these substrates without suffering dewetting from the substrate surfaces, and subsequent thermal annealing enhanced the force through thermal-triggered covalent reaction between the hydroxyl groups of the polymer and the catechols of the polydopamine, which facilitated the further nanopatterning, depending on different requirements (Figure 10B). As proof of concept experiments, Teflon nanowires and a hierarchically organized carbon nanotube (CNT) array directly grown on an Au substrate have been successfully prepared by this method. This procedure has successfully overcome the bottleneck in the case of the performance of devices prepared by previous approaches (Figure 10C,D).

thiol, carboxyl, quaternary ammonium, and catechol groups were easily immobilized on the substrates in a single step. Of particular interest regarding this approach that deserves to be mentioned is that it can be also extended to tailor the properties of superhydrophobic surfaces, which is compatible with the well-established soft-lithographic techniques.138−140 Accordingly, Kim et al. integrated polydopamine-assisted interfacial engineering with block copolymer lithography for patterning substrates with low surface energies.138 The block copolymer lithography technique represents a strong candidate to overcome the intrinsic resolution limitations, an issue that has hampered conventional photolithography. However, patterning aforementioned low-surface-energy substrates with the traditional copolymer lithography technique could hardly be performed, because these substrates do not support organic modification. Kim and colleagues noticed that several typical low-surface-energy materials including cherry tomato, graphene, Au, and even Teflon, which is one of the lowest surface energy materials, could be easily deposited with a thin

4.2. Noble Metal Nanocomposites

The reducing ability of polydopamine toward metal ions suggested the potential preparation of metal nanocomposites 5069


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Figure 11. (A) Schematic procedure for the preparation of polydopamine-Au Janus particles. (B−D) SEM images of polydopamine nanoparticles and the as-prepared polydopamine-Au Janus particles.141 Reprinted with permission from ref 141. Copyright 2012 American Chemical Society.

pH value was in the range of 3.0−3.2, such repulsion was dramatically weakened, leading to irregularly distributed small Au nanoparticles with a diameter of 20−50 nm on the surface of host polydopamine. The as-prepared Janus nanoparticles that combined the unique functionalities of both polydopamine and Au may find potential applications in many fields such as imaging, labeling, catalysis, etc. Generally, polydopamine acts as a versatile interlayer for the modification of various substrates or other nanostructures with metal nanoparticles to impart or enhance some specific functions.142−149 For example, Lee and co-workers utilized its reducing ability for in situ growth of silver nanoparticles on oxides, ceramic, and synthetic polymers as well as with threedimensional self-assembled nanotubes to prepare three-dimensional metal/organic hybrid nanomaterials, and their application as substrates for laser desorption−ionization mass spectrometry (LDI−MS) was investigated.142 Xu and coworkers proposed a new route to fabricate conductive silver films using polydopamine as the adhesive layer.143 In another work, the formation of Pt nanoparticles supported on the surface of polydopamine-modified carbon materials has been reported as useful for catalysis.144 Further, Sureshkumar et al. built up a multilayer of multimetal nanoparticles on the surface of the polymer film with the help of exceptional adhesive and reductive self-polymerized polydopamine, and this hybrid film has demonstrated enhanced antibacterial and catalytic performance.145

that would display the versatile features of polydopamine. A representative example is the direct synthesis of metal nanoparticles. For one thing, the polymerization process of dopamine can reduce the metal ions into metal nanoparticles. In this regard, neither additional reductants nor metallic seed particles are required. Furthermore, the as-formed polydopamine plays an important role in preventing the metal nanoparticles from agglomeration by the quinones and unoxidized catechol groups. For another thing, the obtained polydopamine can serve as both reducing agent of metal ions and anchor for the resultant metal(0). The metal(0) bonds at the N-site and O-site in polydopamine and acted as the seed precursor for the formation of metal nanoparticles via the atomby-atom growth with the continuous reduction of metal ions. Of great interest is the work performed by Wang and coworkers in which the adjustment of the environmental pH could lead to polydopamine-Au particles with different structures.141 Polydopamine nanoparticles with an average diameter of 230 nm were first prepared by oxidation and selfpolymerization of dopamine monomer in an aqueous NaOH solution, and were directly used as the host to synthesize polydopamine-Au particles. Upon consecutive addition of HCl and HAuCl4 to the resultant polydopamine nanoparticle suspension, the rapid reduction of HAuCl4 was observed, and small Au nanoparticles were immediately deposited on the surface of the host polydopamine. The Au nanoparticles grew with time, and their size reached equilibrium (125−250 nm) after 5 min. Interestingly, 90% of the polydopamine-Au nanoparticles were of the Janus type rather than core−shell structures (Figure 11). The yield of polydopamine-Au Janus nanoparticles was noticed to be highly dependent on the pH value of the reaction medium. Only at pH values ranging from 2.5 to 3.0 was it possible to form polydopamine-Au Janus nanoparticles. Because polydopamine is positively charged when pH is lower than 4 as mentioned above, at pH values below 2.3, the electrostatic repulsion between polydopamine and Au3+ ions was so strong that the predominant products were large and separated Au nanoparticles, whereas when the

4.3. Graphene-Based Nanocomposites

Graphene, which is composed of a one-atom-thick planar sheet of carbon organized in a honeycomb structure, has emerged as a rapidly rising star in the field of material science since its discovery in 2004, originated from its unique electrical, optical, thermal, and mechanical properties. Reduction of graphene oxide (GO) is considered to be one of the most efficient tools for the preparation of high-quality graphene.150−152 Nowadays, the reduced GO (rGO) is commonly obtained by ether solvothermally reducing GO in an organic solvent, or chemical 5070


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Figure 12. (A) SEM images of polydopamine-capped GO sheet before and after cross-linking of PEI. Scale bar represents 1 μm in both images. (B,C) Tensile strength and Young’s moduli of the cross-linking polydopamine-capped GO paper, respectively. The digital image of inset in (C) demonstrates that the cross-linked paper strip can support ca. 200 g mass.162 Reprinted with permission from ref 162. Copyright 2013 Wiley-VCH.

modification by other molecules through Michael addition and/ or Schiff-based reaction.161 For example, after modification with amino- or thiol-terminated PEG, the resultant polydopaminecapped rGO can be easily dispersed in various solvents such as CHCl3, DMF, THF, and water with long-term colloid stability, which is essential for the applications of rGO, particularly for bioapplications.155 According to polydopamine chemistry, in a very recent study, Feng and co-workers have further developed a facile method to prepare macroscopic GO papers by controlling the cross-linking reaction between polydopamine on the surface of GO sheets and polyetherimide.162 As compared to previously reported filtration or liquid/air interface self-assembly methods for the preparation of GO papers, such a cross-linking reaction imparted interlayer interactions between the adjacent sheets, thus yielding GO papers with ultrahigh stiffness and higher strength; the Young’s modulus increased by 550%, and the strength was twice that of noncross-linked GO papers (Figure 12). On the other hand, the redox and binding abilities of polydopamine toward metal ions endow rGO with an active surface for further introduction of high-density and dispersed nanoparticles with specific functions on the surface of rGO.163 To date, noble metal nanoparticles, metal oxides, semiconductor materials, as well as hydroxyapatite nanoparticles have been deposited on the polydopamine-capped rGO via in situ nucleation and growth progress of the corresponding precursors under mild conditions (Figure 13). These nanostructures have found numerous applications such as in catalysis, biosensing, antibacteria action, etc., as will be demonstrated below. On the basis of the conspicuous properties of polydopamine, we believe that rGO can be extended to include other types of functionalities for the purpose of finding new properties and will permit the identification of new properties and future applications. Despite the simplicity and versatility of the reductive process, the details of the reduction mechanism still remain ill-defined thus far. Possibly, the release of electrons during the

reduction with toxic or hazardous regents such as hydrazine, NaBH4, and hydroquinone.153 What is worse, the resultant rGO tends to agglomerate irreversibly via the van der Waals interactions if there is no additional stabilizer present in the system.154 For these reasons, great efforts have been devoted to the search for effective and mild routes for the reduction of GO. The redox capacity of dopamine during its polymerization is not restricted to metals alone; it may also offer a new avenue for the large-scale production and stabilization of rGO in one step under mild conditions. The first attempt in this direction was performed by Fu and co-workers in 2010.155 They mixed GO sheets with dopamine in Tris buffer, and the reaction was allowed to proceed at 60 °C under vigorous stirring. As time progressed, the dark brown GO suspension gradually changed into a black solution, implying the reduction of GO. It was noteworthy that this reaction was relatively fast, requiring only 2 h to complete the whole reducing progress of GO, as identified by UV−vis and X-ray photoelectron spectroscopy (XPS) analysis. In fact, later studies have illustrated that such a reduction and functionalization reaction sequence could proceed at room temperature but with a relatively weaker reducing effect.156−160 Both sides of each rGO sheet were capped with polydopamine layers, and the resultant polydopamine-capped rGO sheets had fairly smooth surfaces with a thickness of about 1.25 nm, revealing the well-controlled coating process. In addition, the structures remained stable in water without precipitate for at least 3 weeks due to the stabilization by polydopamine, and rGO could be redispersed by mild sonication for a few minutes. More specifically, the conductivity of the resultant rGO sheets was enhanced to some extent, and further low-temperature thermal treatment or chemical reduction led to highly conductive graphene with electrical conductivity up to 104 S/m.159 Another striking merit of this procedure is that the polydopamine layer on the surface of rGO can facilitate the design of various rGO-based hybrid materials. On the one hand, polydopamine on the surface of rGO supports the second 5071


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Figure 13. (A) Schematic representation of in situ deposition of noble metals, metal oxides, and semiconductor nanoparticles on the surface of polydopamine-capped rGO based on the reducing and chelating ability toward metal ions. (B−G) TEM images of the resultant (B) polydopamine/ rGO, (C) Au/polydopamine/rGO, (D) Ag/polydopamine/rGO, (E) Pt/polydopamine/rGO, (F) Fe3O4/polydopamine/rGO, and (G) TiO2/ polydopamine/rGO, respectively.163 Reprinted with permission from ref 163. Copyright 2012 Royal Society of Chemistry.

synthesis of polydopamine is typically carried out at mild conditions, and their sizes are easily controlled; (ii) polydopamine has a robust chelating capability toward metal ions, which means that adjusting the category of metal or metal oxides can produce polymer−inorganic core/shell structures with tunable functions; (iii) polydopamine can serve either as the active template for the assembling of nanoarchitectures or as the building unit to form a polymer shell on the inorganic or organic nanoparticles; and (iv) under mild conditions, researchers can finely tailor the surface properties of core/ shell nanostructures through adjusting the polydopamine chemistry for specific requirements, when polydopamine acts as the shell. The convenient synthesis of polydopamine/transition metal oxides core/shell nanoparticles is a good example of the use of polydopamine as the active template. The functional groups such as −NH2, −OH on the surface of polydopamine nanoparticles are good ligands for bonding metal ions to yield metal−ligand complex and thus act as nucleation sites for the formation of metal oxide shells. For example, addition of KMnO4 solution into a suspension of polydopamine nanoparticles in the presence of H2SO4 led to uniform polydopamine/MnO2 core/shell nanoparticles, and subsequent addition of KOH gave rise to hollow MnO2 nanospheres. By adding

polymerization of dopamine will attack the oxygen-containing species such as CO in GO, and such an electron transfer process seems to be the key to the complete reduction of the GO. Some researchers have argued that the reduction process of GO at 60 °C follows two steps: SN2 nucleophilic reactions and a subsequent thermal elimination of catechol groups. The first step involves the attack at the epoxy ring or hydroxyl on the GO by catechol groups of dopamine, coupled with release of one H2O molecule. Thermal treatment would result in the elimination of catechol groups, leaving the sp2 skeleton behind, as well as dopamine-quinone, which would further undergo self-polymerization on the surface of rGO.164 4.4. Metal Oxide−Polydopamine Core/Shell Nanostructures

Since the early 1990s, the synthesis and applications of core/ shell nanostructures, particularly polymer-based core/shell nanostructures, have been among the most important areas of nanotechnology research, largely because of the tailored properties, size, structure, and functionalities of the polymers in such systems.165−168 To some extent, polydopamine shows a higher degree of designability and flexibility in the target structures when compared to other polymers. This is mainly attributed to, at least in concept, four aspects as follows: (i) the 5072


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Figure 14. (A) Schematic illustration of in situ formation of catechol-functionalized chitosan/pluronic hydrogel. (B) Digital images of the resultant hydrogel. (C) Photographic images of free pluronic F-127, and hydrogels with different amounts of pluronic F-127 in the subcutaneous region of mice at indicated timed intervals.182 Reprinted with permission from ref 182. Copyright 2011 American Chemical Society.

spheres.379 Other types of metal oxides/polydopamine core/ shell structures including Co3O4, MnO2/polydopamine nanocomposites have also been reported through a similar coating process.177 Each of these two approaches has its own advantages and limitations. For example, the first approach is convenient to synthesize diverse hollow metal or metal oxide nanostructures after the removal of polydopamine. As compared to the first strategy, however, the second approach enjoys at least three striking features. First, the choice of the core materials is much broader, and multicores can be encapsulated in the polydopamine shells, simultaneously. Second, the polydopamine shell can prevent the core materials from interfering in the redox reaction. For instance, pure magnetic nanoparticles have a strong tendency to aggregate and can undergo rapid biodegradation when directly exposed to biological systems. The polydopamine coating can effectively block these particles from direct contact with biological systems and decrease their biodegradation rate. Third, on the basis of the polydopamine chemistry as well as its reducing ability, additional surface modification is much easier and more diversified on the polydopamine shells than on the inorganic core surfaces.

iron ions, on the other hand, polydopamine/Fe3O4 core/shell nanospheres could be obtained through a simple precipitation process.169 With polydopamine nanoparticles as the templates, the as-prepared core/shell nanostructures were uniform and homogeneous. More importantly, this method saves both time and energy as compared to previous approaches for the fabrication of core/shell structures. The reaction was extremely fast and could be completed within several minutes with a high yield. In turn, injection of dopamine solution into a metal oxide suspension can lead to the generation of a polydopamine shell with a controlled shell thickness on the metal oxides, which can be regarded as a “bottom-up” self-assembly procedure. Take Fe3O4 as an illustration again, carboxyl group-functionalized Fe3O4 nanoparticles were prepared through a solvothermal reaction, and their size could be tuned from several to 200 nm by adjusting the reaction conditions.170 Because of the presence of carboxyl groups, dopamine could adsorb on the surface of Fe3O4 nanoparticles by the formation of −COO−NH2− ion pairs, and could undergo self-polymerization under basic conditions to form a polydopamine shell with well-defined core/shell structures. The shell thickness could be finely controlled in the range of 10−25 nm by varying the concentration of dopamine monomer.171 There is no doubt that such a procedure is also applicable to other metal oxides.172−177 For instance, Liu et al. have implemented a similar strategy to synthesize TiO2/polydopamine core/shell spheres and converted these spheres to TiO2/carbon core/shell spheres after thermal annealing.172 Lu and co-workers deposited the polydopamine shell on the surface of SnO2. Chen and co-workers synthesized ZnO/polydopamine microspheres. Subsequently, the template was dissolved in base, and the incorporated Ag+ ion was reduced in situ to produce monodisperse polydopamine/Ag hybrid hollow micro-

4.5. Hydrogels

Hydrogels possess many unique physicochemical properties that are potentially useful in a broad range of applications. They can be used as injectable drug delivery depots, sensors, medical devices, tissue engineering scaffolds, and separation systems.178−180 According to different cross-linking reactions, hydrogels can be categorized into chemical and physical gels. In chemical gels, the subunits are cross-linked through covalent bonding, whereas the subunits in physical gels are held together by various noncovalent interactions involving hydrogen bonds, coordination bonds, π−π stacking, and electrostatic interactions.181 5073


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Figure 15. (A) The cross-linking reaction between catechol groups and Fe3+ ions. (B) The cross-linking reactions in the foot protein of mussels. (C−E) Fe3+ ion triggered the formation of the PEG-dopa hydrogel at different pH values.187 Reprinted with permission from ref 187. Copyright 2011 Proceedings of the National Academy of Sciences.

Fe(III)-mediated coordination cross-linking would be extremely useful for the production of polydopamine-based hydrogels with novel or enhanced properties. This hypothesis was verified in a recent report by Lu’s group. These investigators used polydopamine-modified clay as the building block. In the presence of a small amount of Fe(III) ions, the coordination interaction between the catechol groups of polydopamine on the clay nanosheets and Fe(III) ions drove the cross-linking of clay nanosheets and thereby gave rise to the formation of supramolecular hydrogels.123,189

The cross-linking reactions that trigger the formation of polydopamine-based hydrogels fall into two large categories as well: covalent bonding and noncovalent interactions. In the first strategy, amine- or thiol-terminated molecules are commonly involved as the cross-linking agents based on the Michael addition and/or Schiff base reaction. Alternatively, the crosslinking of dopamine moieties can be induced by oxidizing agents. Initially, researchers designed different dopaminefunctionalized organic molecules such as PEG, chitosan, and hyaluronic acid as cross-linkable moieties, and these moieties could undergo rapid sol−gel transition once in contact with amine- or thiol-terminated molecules.182−184 Furthermore, because of the adhesion ability of catechol, these hydrogels showed strong adhesion to wet mucosal surfaces and tissues, ideal for biomedical applications involving wound healing, surgical tissue adhesives, and tissue engineering (Figure 14). In the second strategy, the catechol-mediated coordination with metal ions is a typical example of noncovalent attraction. A certain amount of Fe(III) has been found in extracts of mussel foot protein and remains tightly bound to the protein even after treatment with strong chelators (EDTA) or acid.185 An early report published by Waite and co-workers demonstrated that mussel foot protein Mfp-1 as well as several oligopeptide fragments of this protein containing the catecholic amino acid 3,4-dihydroxyphenyl-lalanine (DOPA) are able to coordinate with Fe(III), giving rise to bis-catecholato complexes at physiological pH, and tris-catecholato complexes at high pH.186 On the basis of these findings, a range of synthetic molecules that contain catechol groups such as catecholmodified 4-arm PEG and 3,4-dihydroxystyrene have also been studied for the design of a synthetic self-healing hydrogel by applying Fe(III)-mediated coordination cross-linking in a biomimetic fashion (Figure 15).187,188 Presumably, such

4.6. Hydroxyapatite and Calcium Carbonate

During the last two decades, researchers have devoted tremendous efforts to understanding the mechanism of biomineralization in natural systems and have attempted to mimic this process to fabricate novel organic−inorganic hybrid materials with fascinating morphologies, outstanding chemical and mechanical properties, and unique biological functions.190−194 Calcium-based minerals (or their composites) have gained great attention and have been widely studied as carriers for drugs, proteins, and many other bioactive compounds, as they are biocompatible and biodegradable. Hydroxyapatite is a naturally occurring mineral form of calcium apatite with a formula of Ca10(PO4)6(OH)2. It is a major component of hard tissue like bones and teeth in the human body. As a consequence, it has been widely used as a filler to replace amputated bone or as a coating to promote bone ingrowth, and also used for dental implantation.195,196 However, there is a lack of effective methodology that can integrate hydroxyapatites into various synthetic materials to create the next generation of hybrid materials. Inspired by the strong adhesion of the catechol group to a wide range of substances as well as its affinitive interaction with calcium ions, 5074


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Figure 16. (A) Schematic description of the formation of hydroxyapatite crystal biominerals facilitated by polydopamine on substrates. (B) SEM images of unmodified and polydopamine-modified substrates after incubation in a simulated body fluid for 2 weeks, respectively.197 Reprinted with permission from ref 197. Copyright 2010 Wiley-VCH. (C) XRD pattern of polydopamine. (D,E) Structure models of polydopamine and hydroxyapatite nanocrystals, respectively.199 Reprinted with permission from ref 199. Copyright 2011 Royal Society of Chemistry.

substrates, but also offer Ca2+ binding sites for the nucleation of hydroxyapatites on the substrate surface. The unique chemical and mechanical characters of natural bones have been confirmed to be closely associated with the mineralization of c-axis-oriented hydroxyapatite crystals and self-assembled collagen nanofibers at the lowest hierarchical level.198 Such a biomineralization progress has recently stimulated great interest in preparing bone-like nanocomposite materials for biological and biomedical applications, such as tissue engineering. However, it is difficult to synthesize composite materials with a structure similar to that of natural bones. Recently, Park and colleagues found that, with the assistance of polydopamine, peptide/hydroxyapatite nanocomposites with a structure similar to bone tissue could be easily obtained.199 They used self-assembled diphenylalanine nanowires with dimensions similar to those of collagen nanofibers in natural bone as the organic matrix. These nanowires were coated with a 5−10 nm polydopamine layer and then incubated in a simulated body fluid solution at 37 °C for 2 days. Interestingly, selected area electron diffraction and X-ray diffraction (XRD) analysis confirmed that the hydroxyapatite nanocrystals grew only in the orientation of c-axis along the polydopamine-coated peptide nanowires, similar to the

Park and co-workers reported a universal biomineralization route, termed polydopamine-assisted hydroxyapatite formation, to integrate hydroxyapatites within virtually any type of scaffold materials.197 First, various substrates with surfaces composed of different materials including metals (Ti, Au, Si, stainless steel), ceramics (SiO2), semiconductors (Si3N4), and polymers (polystyrene (PS), cellulose, poly(dimethylsiloxane) (PDMS), poly(methyl methacrylate) (PMMA), nylon, polyester, and polytetrafluoroethylene (PTFE)) were coated with polydopamine by simple immersion of the substrates in an aqueous solution of dopamine in tris buffer (pH 8.5). After 16 h of polymerization and washing with water, these polydopaminecoated substrates were transferred into a simulated body fluid (Na+, 213.0; K+, 7.5; Mg2+, 2.25; Ca2+, 3.75; Cl−, 221.7; HCO3−, 6.3; HPO42−, 1.5; SO42−, 0.75 mM) and incubated at 37 °C. After incubation for 2 weeks, these polydopaminecoated substrates were found to be fully and uniformly covered by plate-like hydroxyapatite crystals, regardless of the substrate’s surface property, structure, and morphology, whereas no growth of hydroxyapatite crystals was observed on the untreated substrates over the same time period (Figure 16). This phenomenon implied that the catechol groups of polydopamine not only play the role of molecular anchor for 5075


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XRD analysis showed clear evidence that the as-prepared hollow CaCO3 microspheres had vaterite crystal structure. It is believed that CO2 gas not only provided CO32−, but also served as the reaction template for the formation of hollow CaCO3 vaterite microspheres, with the assistance of polydopamine as the stabilization agents. It is worth noting that the polydopamine-induced CaCO3 vaterite microspheres could be easily converted into bone hydroxyapatites composites in simulated body fluid solution for practical use.207,208

mineralized collagen nanofibers in natural bones. From the viewpoint of structure, although there is still a controversy about the polymerization mechanism, it is generally accepted that polydopamine has an interconnected layered structure similar to naturally occurring eumelanin. The average interlayer spacing of polydopamine was determined to be 3.47 Å, almost equivalent to the distance (3.44 Å) between calcium atoms along the [001] direction of hydroxyapatites (Figure 16C−E). Such closely matched lattices between polydopamine and hydroxyapatites, together with the capacity of polydopamine to capture calcium ions, enabled the specific orientation growth of hydroxyapatites along the polydopamine-coated peptide nanowires. Furthermore, by in situ growth of hydroxyapatites on carbon nanotubes, the strength and toughness of hydroxyapatite minerals were enhanced.200 Another widely investigated biomineral is calcium carbonate (CaCO3). It has three different crystalline phases: aragonite, calcite, and vaterite. Vaterite is the most unstable and easiest to convert into other phases. Nevertheless, it is more suitable for biomedical and industrial applications in principle, because it has higher dispersion and solubility, higher surface area, and a smaller specific gravity as compared to the other two phases. The major hurdle to its practical applications is how to stabilize it.201−203 In nature, the vaterite phase exists stably in pearls that are found in mussels. This indicates that mussels may contain specific biogenic materials responsible for the formation and stabilization of the vaterite phase. Researchers speculated that 3,4-dihydroxy-L-phenylalanine in Mefp-5 protein, an analogue of dopamine, might contribute to the stabilization of the vaterite phase. On the basis of this speculation, researchers further attempted to utilize the polymerization of dopamine to synthesize stable vaterite.204,205 Dopamine was first dissolved in tris buffer (pH 5) and allowed to polymerize for 2 min. To initiate the mineralization progress of CaCO3, the prepolymerized dopamine solution was mixed with Na2CO3 and CaCl2 in aqueous solution, and the resultant mixture was allowed to proceed under mild stirring for 4 days. The resultant precipitates were observed to have spherical morphology with diameters ranging from 3 to 10 μm, and their XRD diffraction peaks were well indexed to the vaterite structure. Moreover, the vaterite was quite stable without any phase transition even after 2 months. In the absence of dopamine, however, CaCO3 precipitates typically showed large rhombohedral (25 μm) calcite crystals and substantial growth of calcite crystals when redispersed in a dopamine-free system. These authors proposed the following mechanism based on these results: (1) the polymerization of dopamine monomer into polydopamine during the mineralization facilitated the formation of vaterite phase; and (2) the strong binding capacity of catechol groups to calcium ions, in turn, further blocked the phase transition and retarded the dissolution of vaterite phase. However, the detailed mechanisms associated with the formation and stabilization of vaterite phase still remain unclear. In a later publication, Park and colleagues further reported a CO2-consuming pathway to prepare hollow CaCO3 vaterite microspheres based on the above phenomenon.206 Different from the above method, CO2 gas was used in this study as the consumable resource of CO32− instead of NaCO3. After the continuous introduction of CO2 gas for 1 h into an aqueous solution containing CaCl2, NH4OH, and dopamine, hollow CaCO3 microspheres with an average size of 5 μm were formed. Furthermore, the outer shell of the hollow CaCO3 microspheres was porous with a mean pore size of 13.78 nm.

4.7. Synthetic Membranes

Synthetic membranes, such as microfiltration, nanofiltration, ultrafiltration, and reverse osmosis membranes, are applied in many fields ranging from chemistry and biology to industry.209 However, poor hydrophilicity and biofouling have been the major problems affecting their practical applications. A decrease in water flux and the development of biofouling caused by the accumulation of microorganisms are unavoidable side effects generated when synthetic membranes are used in water treatment, blood-contact devices, etc., because these filtration membranes are typically composed of hydrophobic polymers that are highly prone to interact with the organic contaminants.210,211 A straightforward way to increase the hydrophilicity and combat membrane fouling can be attained through postmodification of these membranes, but there is a lack of a general surface modification technique that is applicable to all kinds of membranes. It is evident that the nonspecific adhesion and high hydrophilicity of polydopamine may provide a great opportunity for this purpose, and the use of polydopamine in the membrane field has also increased.212−225 In 2010, Freeman and co-workers reported an overview of the influence of polydopamine deposition conditions on the pure water flux and fouling resistance for reverse osmosis, ultrafiltration, and microfiltration membranes.216 These authors pointed out that polydopamine-coated membranes displayed high resistance to protein adhesion because polydopamine coating imparted strong hydrophilicity on membranes while minimizing the hydrophobic−hydrophobic interactions between the membrane and proteins, an outcome ascribed to the hydrogen bonding between the catechol groups of polydopamine and water molecules. Grafting PEG onto the polydopamine-coated membranes could lead to further enhancement of biofouling resistance.212 Responding to these results, Miller et al. quantitatively determined the enhancement effect of polydopamine on the fouling resistance of membranes by fluorescence technique.225 They decorated the polydopamine coating with the fluorescent dye-labeled BSA, and explored the fluorescence intensity of these membranes in the presence of foulants. It was observed that the fluorescence intensity of polydopamine-modified membranes was 2 orders of magnitude lower than that of pristine membranes, and the fluorescence intensity was reduced even further when PEG was grafted onto the polydopaminecoated membrane. Additionally, both polydopamine- and polydopamine-PEG-modified membranes were capable of reducing protein and bacterial binding during the short-term adhesion tests. However, long-term continuous biofouling tests demonstrated that polydopamine or polydopamine-PEG coatings did not effectively control biofouling. Thus, the improvement of the long-term biofouling of polydopamine-coated membranes is still a significant issue facing membrane techniques. 5076


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Figure 17. (A) Schematic illustration of the modification of PS-b-P4VP membranes. (B) Photograph of polydopamine-modified membranes after different deposition time. (C,D) SEM images of the bare PS-b-P4VP membrane and the PS-b-P4VP membrane modified with polydopamine and pNIPAMNH2, respectively. (E−G) Contact angle measurements of water droplets (5 μL) onto PS-b-P4VP membrane, PS-b-P4VP membrane after polydopamine coating, and PS-b-P4VP membrane after polydopamine coating and reaction with pNIPAM-NH2, respectively.226 Reprinted with permission from ref 226. Copyright 2013 Wiley-VCH.

interlayer (Figure 17).226 The PS-b-P4VP membranes exhibited an interesting effect on water flux measurements: they were capable of closing their pores when the pH value was lowered through swelling of the P4VP block, whereas an elevation in the pH value would result in a reversible opening of these pores. After modification with temperature-responsive pNIPAM, water flux measurement showed a steady increase in the water flux as the temperature increased over the range of 3−45 °C because of the regular improvement of the permeability at higher temperatures. Such a double stimuli-responsive property may find promising applications such as for biomolecule separations.

Besides long-term biofouling, of equal concern is that membranes may lose their water flux after polydopamine coating due to the coating-induced pore blocking of these membranes; this phenomenon will become more significant when the deposition time of polydopamine is prolonged. To efficiently avoid this phenomenon, Zhao and co-workers preintroduced a pore-forming agent PES-PEG1000 to the polyethersulfone (PES) ultrafiltration membranes before polydopamine coating, and investigated their characteristics of hydrodynamic permeability, surface property, and blood compatibility in detail.215 The introduction of PES-PEG1000 could effectively inhibit the pore blocking, and polydopaminecoated membranes displayed a high water flux capability that can meet the industrial or clinical requirements, even with 24 h of polydopamine deposition. The addition of functionalized molecules on the surface of synthetic membranes may extend their use to new applications. However, conventional techniques for membrane surface modification suffer from a lot of shortcomings, such as the requirement of complicated, aggressive surface pretreatment processes, or specific chemistries to graft hydrophilic moieties to the surfaces of membranes. Even worse, some special polymeric membranes are less likely to impart antifouling using these conventional surface modification techniques. On the contrary, polydopamine confers a nonspecific vehicle for the conjugation of interesting molecules. Very recently, Abetz and co-workers prepared double stimuli-responsive porous membranes via modification of pH-sensitive integral asymmetric polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) diblock copolymer membranes with temperature-responsive poly(Nisopropylacrylamide) (pNIPAM) using polydopamine as an

4.8. Polydopamine Microfluidic System

Microfluidics is defined as a multidisciplinary technology used to deal with the behavior, precise control, and manipulation of fluids that are geometrically confined to a small, typically submillimeter, scale. This technology provides a lot of benefits for many research fields, and microfluidic devices can be used for the synthesis of monodisperse particles, protein crystallization, biological assays, and so on.227,228 Among them, 2D microfluidic devices, also called “surface-tension-confined microfluidic” (STCM) devices, can offer a low-energy approach for the transport of fluids, because they depend on the alternating patterns of hydrophilic and superhydrophobic areas to self-drive or guide the liquid by virtue of the capillary force within the hydrophilic region.229 However, this methodology suffers from poor long-term stability and loss of fluids resulting from the retention of a small amount of moving fluids in the hydrophilic regions. Furthermore, it is difficult to create permanent hydrophilic micropatterns on the superhydrophobic surfaces. In pursuit of addressing these issues, in 2010, Lee and 5077


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co-workers were the first to use polydopamine as the hydrophilic area in these devices.230 As shown in Figure 18,

and biodegradation.231−233 Polydopamine is a major component of melanin in organism; the fabrication and utilization of biocompatible polydopamine capsules have thereby become rapidly growing areas of research in the biological and biomedical sciences. To date, procedures for the fabrication of polydopamine capsules have been based on template approaches. In the early stage, the used templates have been focused on monodispersed solid nanoparticles, as these “hard” nanoparticles allowed for a better control over the morphology, size, composition, as well as the final properties. For example, Caruso and co-workers used silica as the hard template to prepare hollow polydopamine capsules.234 Briefly, a polydopamine film was first deposited on the surface of silica by the oxidative self-polymerization of dopamine in Tris buffer (10 mM, pH 8.5). Polydopamine capsules were then obtained after removal of the silica template by etching of a hydrofluoric acid/ ammonium fluoride solution, without incurring any structural damage. The diameter of the resultant polydopamine capsules could be finely controlled over a size range from hundreds of nanometers to several micrometers by tuning the size of the silica nanoparticles, and their wall thickness showed a trend of gradual increase as the polymerization time was prolonged. Moreover, using mesoporous silica as the template, polydopamine capsules with varied porosity could also be obtained. In a later publication, the same group extended this procedure to the fabrication of enzyme-degradable capsules through assembling poly(L-glutamic acid)-conjugated dopamine onto the surface of silica, followed by the removal of the silica core.235 Thereafter, Zhou and co-workers substituted polystyrene for silica as the sacrificial template, and also successfully constructed polydopamine microcapsules through an analogous polydopamine deposition process, which was accompanied by etching the polystyrene core with tetrahydrofuran.236 This concept has been taken further by other researchers, who managed to create polydopamine capsules with CaCO3 as the sacrificial template.237,238 In detail, CaCO3 microspheres with an average diameter of 3 μm were first synthesized by a coprecipitation method. During the coprecipitation process, poly(sodium 4-styrenesulfonate) (PSS) was added to control the size of CaCO3 microspheres, and also to render the surface of CaCO3 microspheres with negative charge. The resultant PSS-stabilized CaCO3 microspheres were subsequently dispersed into the Tris-HCl buffers containing different concentrations of dopamine. The positively charged dopamine was attracted by the negatively charged CaCO3 microspheres through electrostatic interaction, thus triggering the deposition of polydopamine film on the surface of CaCO3 microspheres. After dissolution of the CaCO3 cores with EDTA, uniform polydopamine microcapsules could be successfully acquired. With this facile strategy, different enzymes were separately immobilized through physical encapsulation in the lumen, allowing in situ entrapment within the wall and covalent attachment to the outer surface of the polydopamine capsules under extremely mild conditions, which offered an important platform for many bioapplications. While hard template approaches have been quite successful in producing uniformly sized polydopamine capsules, their use is complicated by the requirement to use and subsequently remove the hard templates by harsh chemical reagents (e.g., acids, organic agents). This may also impose some limits with respect to the applications of polydopamine capsules in which chemically sensitive materials are present. To address these issues, soft template synthesis routes have been therefore

Figure 18. (A) Schematic description of the fabrication of the polydopamine microfluidic device. (B) A representative application of such a polydopamine microfluidic device in chemical reactions.230 Reprinted with permission from ref 230. Copyright 2012 Wiley-VCH.

the device was fabricated by patterning kinked polydopamine microlines with a width of 60 μm on the anodized aluminum oxide surfaces through polydopamine decomposition combined with photolithography. The remarkable adhesion of polydopamine rendered a stable hydrophilic region. When water was dropped on the resultant polydopamine microfluidic device and then the device was tilted downward, the water droplet was observed to move along the polydopamine microlines under gravity. The contact angle of the water droplet on these polydopamine microlines reached as high as 155 ± 2°. Such a high contact angle minimized the dragging force and left no residual traces of solutions in the polydopamine microlines. As illustrations of its versatility, this polydopamine microfluidic system was successfully applied to unfold complex chemical reactions, to synthesize gold nanoparticles, and to the denaturation kinetics of protein by spatially controlling the pattern of polydopamine microlines as described in Figure 18. This polydopamine microfluidic device represents the first example of a microfluidic device without the requirement of an external energy input, and thus holds great promise as a new generation of pump-free microfluidic systems for various applications. 4.9. Polydopamine Capsules

The fabrication of polymer capsules with well-defined structures is an important aspect of investigations in the field of materials science. In particular, the preparation of naturally occurring polymer-based capsules is of great interest in biomedicine because they exhibit excellent biocompatibility 5078


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Figure 19. (A) Schematic representation of the preparation of polydopamine capsules. (B) TEM image of Fe3O4 nanoparticle-loaded polydopamine capsules. (C) Photographs of Fe3O4 nanoparticle-loaded polydopamine capsules dispersed in water before and after applying a magnet. (D) TEM image of QD nanoparticle-loaded polydopamine capsules. (E) The corresponding fluorescence image.239 Reprinted with permission from ref 239. Copyright 2010 Wiley-VCH.

interface can enrich OH ions in the absence of surfactants under certain circumstances, leading to a much higher pH value at the oil/water interface than that in the bulk water. For instance, when the pH of the bulk water is 9, the pH value at the hexadecane/water interface can be up to 14.240 Inspired by this peculiar surface chemistry characteristic, Wang and coworkers utilized the alkane-in-water emulsions as the soft template to prepare polydopamine capsules.241 They noticed that, in the presence of oil, NaOH, and water, dopamine primarily polymerized at the formed oil/water interface instead of undergoing self-polymerization in the bulk water phase when the pH of the emulsion was adjusted to 8.2, regardless of the chemical nature of the oil phase. A possible mechanism for this phenomenon considers that the surface of the pristine oil-inwater emulsion droplet has a pH much higher than that of the bulk water phase, which allows preferential self-polymerization of dopamine on the surfaces of the alkane droplets. Besides, the strong interfacial basicity of pristine oil-in-water emulsion droplets can deprotonate the polydopamine chains and make them more hydrophobic, because the pKa of the amine group of dopamine is lower than that at the interface. Thus, the hydrophobic interaction between the oil phase and deprotonated polydopamine chains also contributes to the selective growth of the polydopamine shells on the droplet surfaces. Seeking to shorten the preparation time, Rahimipour and coworkers recently combined this soft emulsion method with a simple sonochemical approach to prepare polydopamine capsules.242 Briefly, a basic solution of dopamine in tris buffer (pH 8.5) was mixed with canola oil or n-dodecane, and this mixture was exposed to high intensity ultrasonic waves at an acoustic power of 150 W/cm2. Only 12 min of irradiation could generate polydopamine nanocapsules, in marked contrast to 24 h often required for classical emulsion methodology; this duration could be further reduced to 6 min when Cu2+ ions were present, because Cu2+ ions are capable of accelerating the polymerization of dopamine.

proposed to produce polydopamine capsules. The earliest report involving the use of soft template synthesis routes for the production of polydopamine capsules appeared in 2010.239 In that work, monodisperse and stable emulsion droplets were first formed by the hydrolysis and partial condensation of dimethyldiethoxysilane (DMDES) in aqueous ammonia solution. The resultant DMDES emulsion droplets were then used as the soft templates for the direct deposition of polydopamine (Figure 19). Similar to solid particles, the size of the emulsion droplets could be tailored over a range of hundreds of nanometers to several micrometers only by varying the condensation time or the concentration of DMDES. After controllable polymerization of dopamine on the surfaces of the emulsion droplets, the as-formed polydopamine-coated emulsion droplets could be isolated by centrifugation, and the emulsion templates were easily removed by washing with ethanol two times to give the final polydopamine capsules, eliminating the need for harsh chemical agents. This facile strategy also demonstrated the first example of uniform and monodisperse polymer capsules with tailored size and wall thickness prepared from emulsion templates. More specifically, functional hydrophobic cargo such as oleic acid-stabilized magnetic nanoparticles, fluorescent semiconductor quantum dots, and hydrophobic anticancer drugs could be preloaded during the formation of emulsion droplets, and remained encapsulated in the final polydopamine capsules after the removal of templates. It is worth noting that both the polydopamine capsules and the cargo-loaded polydopamine capsules remained stable in water without suffering from any aggregation for a long time. Along with the excellent biocompatibility of polydopamine, this simple and versatile method provides important new tools for some crucial biomedical applications such as targeted imaging and drug delivery. The second potentially useful soft template technique for the fabrication of polydopamine capsules is based on pristine oil-inwater emulsions. It has long been known that the oil/water 5079


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Figure 20. (A) Schematic illustration of the synthesis of polydopamine submicrometer spheres. (B) Typical TEM image of polydopamine submicrometer spheres with an average diameter of 380 nm. (C−H) SEM images of polydopamine submicrometer spheres with different diameters.249 Reprinted with permission from ref 249. Copyright 2013 Wiley-VCH.

properties, such as electric conductivity, thermal conductivity, chemical stability, and low density. These properties, to a great extent, are highly dependent on the characters of their carbon precursors.244,245 Currently, phenol/formaldehyde resins are viewed as potentially valuable carbon resources for preparing carbon spheres, because they are easy to prepare, have high thermal stability, and readily convert into carbon materials.246,247 However, many practical applications of phenol/ formaldehyde resins-derived carbon spheres are limited in scope because they require the use of strongly carcinogenic phenol/formaldehyde and they suffer from inaccessibility to the requested performance index in certain fields. Thus, it is highly challenging but desirable to search for new polymer analogues as carbon resources to improve the properties of the final carbon spheres. In context of carbon sphere chemistry, polydopamine has been proposed as an alternative material in the preparation and applications of carbon spheres because it has excellent biocompatibility, nearly 60% of carbon yield under N2 at 800 °C, and has a structure similar to that of phenol/ formaldehyde resins. Without question, the aforementioned template methods for the manufacture of polydopamine capsules are also very elegant tools to create hollow carbon spheres via carbonization followed by removal of the template cores. First evidence of the high potential of such methods was given by Dai and his colleagues in 2011, who utilized polydopamine as the carbon precursor and silica nanospheres as the sacrificed template to produce uniform hollow carbon spheres.248 After carbonization and removal of the silica, the resultant carbon materials appeared to preserve the structural integrity and spherical

A slight, but non-negligible shortcoming of both the hard template and the soft template methods is that the resultant polydopamine capsules are fragile and prone to folding, even undergoing distortion or collapse, after removal of the templates or during subsequent treatment processes. These problems may be overcome by constructing a type of template that intrinsically possesses the capsule structure, and it can also encapsulate functional species, simultaneously. With this type of material, it would be unnecessary to remove the template, thus assuring the integrity of the polydopamine capsules. For example, Städler and colleagues combined the striking properties of polydopamine with the unique hollow structure of liposome to prepare multifunctional liposome-containing polydopamine capsules.243 In that work, an amphiphilic molecule (oleoyldopamine) with dopamine as the hydrophilic head was synthesized; when mixed with another amphiphilic molecule, these two amphiphilic molecules underwent selfassembling into liposomes. In addition to electrostatic interaction, the embedding of oleoyldopamine within the membrane of liposomes served as an anchor to facilitate the polydopamine deposition as it could copolymerize with the dopamine under basic condition. With this method, the resultant capsules remain intact without suffering distortion or damage of the membrane, and remain stable for at least 2 weeks. 4.10. Carbon Materials

Monodispersed carbon spheres have found widespread use in drug delivery, catalysis, energy storage, and active material encapsulation. Their successful use in such diverse applications is directly related to their superior physical and chemical 5080


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Figure 21. (A) Schematic description of the preparation of flexible transparent and conductive pyrolyzed polydopamine films. (B) Typical TEM image of the as-prepared pyrolyzed polydopamine films. (C) Photographic images of patterned pyrolyzed polydopamine film on PET and PDMS, and flexible photodetector on PET substrate with pyrolyzed polydopamine as the electrode. (D) I−V characteristics of the pyrolyzed polydopamine film-derived photodetector. (E) The on/off characteristics of the photodetector in the flat and bent state.250 Reprinted with permission from ref 250. Copyright 2013 Wiley-VCH.

presence of high-level electroactive nitrogen species in the carbon matrix of the polydopamine-derived carbon submicrometer spheres due to the presence of nitrogen in their starting materials (polydopamine), which would be highly beneficial for improving the material’s performance as compared to the nitrogen-free phenol/formaldehyde resinderived carbon spheres. Finally, because polydopamine inherits many functional groups such as catechol and N−H groups from their starting material, this facile strategy provides new avenues for the preparation of various hybrid materials with specific properties. On the basis of the obtained graphitic structure upon thermal treatment, very recently, Li et al. introduced a clever design for a synthetic route for the wafer-scale production of a highly stretchable and conductive carbon film.250 In detail, the target substrates were immersed in a Tris buffer of dopamine for the desired time to deposit a polydopamine film, and then placed in a tube furnace for thermal treatment under a hydrogen atmosphere to obtain the conductive carbon film (Figure 21). With this procedure, the conductivity of the resultant carbon film obtained at a thermal treatment temperature of 1000 °C was as high as 1200 S/cm, which was comparable to that of polycrystalline graphite (1250 S/cm) and even higher than that of rGO (727 S/cm) as well as pyrolyzed polycyclic aromatichydrocarbon (206 S/cm). Furthermore, this carbon film could be easily transferred onto other substrates by using sacrificial metal foils as the underlying substrate, and patterning the carbon film on polyethylene terephthalate (PET) or polydimethylsiloxane (PDMS) led to a flexible photodetector. When a bias voltage was applied, this device could give fast and repeatable responses to light and did not suffer from obvious change in light response, even after 100 cycles of bending, indicating the great promise of the carbon film as a flexible electrode.

morphology. More interestingly, this facile process can also be conveniently applied to synthesize other carbon-coated composites. As a demonstration of its versatility, the authors took use of Au@SiO2 core−shell nanoparticles as the template instead of single SiO2 nanospheres. Following a similar procedure, a thin polydopamine shell was coated on the Au@ SiO2, and the subsequent carbonization and HF etching gave rise to the Au@C nanorattle structures, which showed a faster catalytic rate than the previously reported Au@SiO2 and Au@ polymer nanorattle structures with catalytic stability in the reduction reaction of 4-nitrophenol. The major drawback of this approach, however, lies in the requirement for a multistep synthesis procedure and the use of highly toxic HF to remove the template, which may place some limitations on the practical use of these hollow carbon spheres. Very recently, Lu and his colleagues described a new synthesis pathway for the generation of monodisperse and size-controlled carbon submicrometer spheres.249 These authors found that dopamine could directly polymerize into polydopamine submicrometer spheres in a mixture containing water, ethanol, and ammonia at room temperature, without the need for any template (Figure 20). After carbonization at 800 °C, the assynthesized polydopamine submicrometer spheres were directly converted into carbon submicrometer spheres without any change in morphology. Furthermore, their size could be precisely adjusted over a wide range by varying the ratio of ammonia to dopamine, even to sizes below 200 nm. The precise control of particle size has long been a big challenge in the synthesis of uniform carbon spheres. More specifically, as compared to the carbon spheres obtained by carbonization of phenol/formaldehyde resins, the polydopamine-derived carbon submicrometer spheres contained nearly 100% of sp2 C (graphitic carbon), thus exhibiting enhanced electroconductivity. Another remarkable difference between them is the 5081


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Figure 22. (A,B) Photographic images of the PE separator before and after polydopamine coating, respectively. (C,D) SEM images of the PE separator before and after polydopamine coating, respectively. (E,F) Surface property changes of the PE separator before (left) and after (right) polydopamine coating. (G) Voltage profiles of the pouch-type half cells with and without polydopamine coating during the first cycle. Both cells were cycled at a rate of 0.1C between 3.0 and 4.5 V. (H) Discharging capacities of both types of cells at a series of current densities. The voltage range for these measurements was between 3.0 and 4.5 V. (I) Nyquist plots for the pouch-type half cells after 70 cycles shown in (H).255 Reprinted with permission from ref 255. Copyright 2011 Wiley-VCH.

5. APPLICATIONS IN ENERGY Presently, improvements in the utilization ratio of fuels and exploration of new energy resources are envisioned to be the two best ways to solve the potential energy crisis. Despite being at a relatively early stage, polydopamine has showed many potentially exciting applications in these research fields. Most work in these directions has concentrated on the utilization of striking properties of polydopamine including the high carbon yield, robust wetting and adhesion capabilities, as well as its behavior as a reducing agent. This section presents the contributions of polydopamine in applications for the generation of new energy sources.

battery operations, as the components constituting a Li-ion batteriers are in contact with each other within the liquid environments. At present, Li-ion batteries have rapidly spread into varieties of portable electronics applications. Nevertheless, significant improvements in their performance including energy and power density, cycle life, and safety reliability are highly desirable, particularly for future emerging markets.251−253 An essential component, the separator, is usually made of porous polymers and has a serious effect on the performance of batteries, especially the power capability. Currently available polyethylene (PE) separators have a hydrophobic surface and low surface energy, factors that severely hinder the adequate diffusion of liquid electrolyte within the separators and thus directly impair the power performance and cycle life of the battery.254 Inspired by the versatile and wet-resistant adhesion ability of polydopamine, Choi and co-workers developed a simple dipping process to modify the PE separator with polydopamine to overcome the poor compatibility of the PE separator with liquid electrolytes.255,256 This facile strategy avoids some of the inevitable adverse effects generated in previously reported coating processes, such as the deterioration of the high-power capabilities due to the pore blocking of the separator, the environmental problems caused by the use of toxic organic

5.1. Batteries

5.1.1. Li-Ion Batteries. Thorough investigations of mussels have revealed that the catechol functional group plays a crucial role in their powerful adhesion capability on various surfaces, even on wet surfaces. The same holds true for polydopamine with similar functional groups. These significant findings are of great significance not only because of providing a convenient route to synthesize various functionalized substrates, but also because they offer opportunities for improving the performance of materials. In fact, the strong and robust wet-resistant adhesion of polydopamine may be highly beneficial for Li-ion 5082


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of the polydopamine modification can explain these results. First, the favorable hydrophilicity and wetting-resistance of polydopamine allow uniform Li ionic flux and thus effectively prevent Li ions from localized reaction on the surface of the Li metal. Second, the strong and robust adhesion of polydopamine could strengthen the interaction between the Li metal and the PE separator and reduce the surface tension of the Li metal, which made the initiation of the Li dendrites formation fairly more difficult. In addition to hydrophobicity, another major concern associated with the bare PE separators is their intrinsic thermal shrinkage problem at high temperatures, which shortens the distance between the anodes and cathodes, and eventually causes cell explosion. Polydopamine coating could mechanically stabilize the whole framework of the PE separators. Along with the high thermal stability of polydopamine itself, the polydopamine-modified PE separators only showed 16% of dimensional shrinkage after thermal treatment at 140 °C for 1 h, revealing their enhanced resistance against thermal shrinkage. In contrast, the bare PE separator suffered up to approximately 33% of dimensional shrinkage after the same treatment. Aside from restraining the growth of Li dendrites, numerous efforts have been devoted to the search for alternative anode materials as a substitute for the Li metal. Graphitic carbon is the most widely used anode material in commercial Li-ion batteries, as it is cost-effective and quite safe due to its negligible volume change upon full lithiation. Unfortunately, its low theoretical capacity limits its extension to the Li-ion battery applications. Metal or metal oxides such as Sn, Si, and Fe3O4, with higher theoretical capacity and low cost, have been recognized to be promising candidates as next-generation anode materials for Liion batteries.260−262 Nevertheless, their practical use is still hampered by their low conductivity as well as severe aggregation and significant volume expansion during Li+ insertion/extraction processes, which results in pulverization of the electrodes and rapid capacity decay. One of the most effective strategies to tackle these problems is to coat these materials with highly conductive carbon shells.263 However, the challenge of achieving carbon layers that feature high conductivity, uniformity and continuity, controllable thickness, and a layered structure similar to that of graphitic carbon on the surfaces of these materials remains unmet. As discussed above, dopamine can self-polymerize and has a strong inclination to spontaneously deposit conformal polydopamine films on virtually any surface under basic condition, and together with its ability to bind strongly to many types of metals, it is possible to form a uniform and continuous polydopamine layer on the surfaces of these metal/metal oxides. These novel materials are then easily converted into highly conductive graphiticstructured carbon materials after thermal treatment. Furthermore, the control over the thickness of the carbon layer can be easily achieved by tuning the concentration of the starting material and the polymerization time. On the basis of these merits, Lu and co-workers reported a novel method to prepare uniform carbon-coated nanosized Fe3O4 (Fe3O4@NC) composites through coating uniformly rhombic-shaped Fe2O3 with polydopamine followed by thermal annealing at 500 °C.264 By fairly controlling the thickness of carbon layer, the Fe3O4@NC composites with a 10 nm thickness of the carbon coating layer exhibited high specific capacity (>800 mA·h/g at 500 mA/g), superior rate capability (595 at 1000 and 396 mA·h/g at 2000 mA/g), and excellent cycling performance (with 99% capacity retention after 200 cycles). Besides Fe3O4, other types of

solvents, high cost, the need for complex instruments, and multistep procedures. After polydopamine modification, the morphology and porous structure of the PE separator remained almost unchanged, while the contact angle of the PE separator was significantly decreased to 39° ± 1.7° as compared to the bare sample (108° ± 1.4°), indicating that the surface of the PE separator becomes highly hydrophilic (Figure 22). After dropping a liquid electrolyte, even a mixture of several liquid electrolytes or those that are not compatible with the bare PE separator, on its surface, the modified PE separator was immediately fully wetted, whereas the bare PE separator appeared to repel the electrolyte and the droplets could be observed on its surface. Benefiting from this enhanced hydrophilicity, the uptake amount of the electrolyte was determined to increase from 96% ± 3.2% to 126% ± 2.8% with the polydopamine-modified PE separator, which was accompanied by an increase of ionic conductivity from 0.23 × 10−3 to 0.41 × 10−3 S/cm. As a result, the battery performance was strongly improved. After assembling pouch-type half-cells (LiMn2O4/separator/lithium metal), the hydrophilic surface effect of the separator on the battery performance was quite evident. At a current density of 15C (1824 mA/g), the discharging capacities of the modified PE cells could maintain 84.1% of the discharging capacities at 1C (121.6 mA/g). In contrast, the bare PE separator cells only showed 46.1% of the capacity retention as the discharging current density increased from 1 to 15C due to their low ionic conductivity. Subsequent studies carried out by Choi’s group have further confirmed that polydopamine can not only strongly improve the wetting ability of the separators, but also with the polydopamine-modified separators, the Li dendrites growth on the surface of Li metal can be efficiently restrained.257 Li metal is well accepted as the best anode material due to its unprecedented theoretical capacity (3860 mAh/g) and electrochemical potential (−3.04 V vs standard hydrogen electrode). However, it is less likely to form a stable solid-electrolyteinterphase (SEI) layer on the surface of Li metal, resulting in the growth of Li dendrites in an uncontrollable manner during the charging processes at high current rates.258,259 The continual growth of Li dendrites can exhaust the lithium ions as well as the electrolyte, which will cause poor cycling performance of the batteries. Even worse, when Li dendrites grow to a certain degree, they often break away from the surface of Li metal and thereby induce a security threat. It has been found that the polydopamine-modified PE-assembled cells exhibited a higher Coulombic efficiency (CE) (97.1%) than both the bare PE cells (91.3%) and the gel polymer electrolyte (GPE) cells (94.1%) during the first cycle. Furthermore, the cycle performance of the cells was also superior to that of the previously reported results. After 100 cycles, the polydopaminemodified PE cells displayed higher capacity retention with 94.9% of the initial discharge capacity maintained at a charging rate of 0.85 mA/cm2, about 8 times larger than that used in previous work, whereas the GPE cells lost 46% of their initial discharge capacity over the same number of cycles, and the bare PE cells even lost their entire discharge capacity only after 30 cycles. The excellent cycle life of the polydopamine-modified PE cells also clearly made them the best Li metal-based cells. Subsequent investigations illustrated that the polydopaminemodified PE separator was helpful for Li metal to form a more stable SEI layer and restrained the Li dendrites growth during charge/discharge processes, which facilitated the transfer of more-efficient Li ions at the interfaces. Two major advantages 5083


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Figure 23. (A) Schematic representation of the application of Si@void@C for Li-ion battery. (B) In situ TEM images of Si@void@C during lithiation/delithiation. (C) Delithiation capacity and CE of the first 1000 galvanostatic cycles between 0.01−1 V (alginate binder). The rate is C/10 for one cycle, then C/3 for 10 cycles, and 1C for the later cycles. (D) Voltage profiles plotted for different cycles. (E) Galvanostatic cycling of different silicon nanostructures (PVDF binder). All samples are cycled at C/50 for the first cycle, C/20 for the second cycle, and C/10 for the later cycles.267 Reprinted with permission from ref 267. Copyright 2012 American Chemical Society.

and his colleagues provided important evidence for the preserved layered structure of carbonized polydopamine from polydopamine as well as its contribution to the cycling stability.271 In this work, carbonized polydopamine-coated SnO2 nanoparticles were used as the Li-ion battery anode material. The TEM image of the polydopamine coating on the SnO2 nanoparticles clearly confirmed the layered structure of the polydopamine coating, and the layered structure could be well retained after thermal treatment. The interlayer spacing was about 0.4 nm for polydopamine coating and 0.37 nm for the resultant carbon coating, highly consistent with the XRD studies. In combination with the XPS analysis and considering the presence of N species, the carbonized polydopamine was regarded as a heteroatom-doped multilayered graphene. The unique structural character determined its high conductivity, restrained the volume expansion, and prevented SnO2 nanoparticles from aggregating during the charge/discharge process, features that led to the superior cycle life of carbonized polydopamine/SnO2 as compared to the pristine SnO 2 nanoparticles. Indeed, without the need for additional carbonization, polydopamine, as a soft and elastic polymer, can intrinsically allow for a relatively large volume change arising from the contraction and expansion of active materials through adjusting its own elastic deformation, thereby releasing partial pressure of active materials during the charge/discharge process.102,272,273 For instance, Jin and co-workers put forward a novel rGO/ SnO2 aerogel-based anode material where polydopamine and poly(acrylic acid) (PAA) were used as buffer layer and binder, respectively.102 The following aspects were summarized to elucidate the reasons for choosing polydopamine as the buffer layer as well as its important roles in the whole electrode

inorganic nanoparticles encapsulated in a polydopaminederived carbon shell have been also prepared by other groups for lithium ion battery anodes.265−269 Si has been widely accepted as one of the most attractive candidates for battery anode materials, as it possesses a high theoretical specific capacity of 4200 mA·h/g, which is over 10 times higher than that of graphite.261 However, its intrinsic drawbacks such as low conductivity and extremely fast capacity decay in cycling tests arising from extremely large volume expansion (300%) during lithiation/delithiation are still the greatest obstacles to the practical use of Si as the anode material.270 In the work performed by Cui’s group,267 Si nanoparticles with an average diameter of 100 nm were first encapsulated in a silica shell, followed by deposition of a polydopamine shell. The subsequent thermal treatment and removal of silica led to a Si@C “yolk-shell”. The well-defined void space within such a “yolk-shell” structure allowed the Si nanoparticles to expand freely without breaking the outer carbon shell, thereby delivering high capacity (2800 mA·h/g at C/10), long cycle life (74% capacity retention after 1000 cycles), and high Coulombic efficiency (99.84%) (Figure 23). Complementary to this work, Lu and his colleagues encapsulated the silicon nanoparticles in hollow graphitized carbon nanofibers derived from polydopamine.265 Electrochemical measurements showed that the resulting C−PDA−Si nanofibers also exhibited cycling stability with capacity as high as 1601 mA·h/g after 50 cycles. It was believed that the excellent electrical conductivity as well as the preserved layered structure and N-dopant of the carbonized polydopamine shell played critical roles in the improvement of cycling performance. By additional studies based on TEM, X-ray diffraction (XRD) analysis, and a series of electrochemical experiments, Lu 5084


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system. First, as discussed above, the intrinsic elasticity of polydopamine is beneficial in allowing rGO/SnO2 composites to release their partial pressure during Li insertion/extraction. A second advantage involves preventing the direct contact between the active material and the electrolyte, thus eliminating the occurrence of side reactions at the electrode−electrolyte interface. The third benefit of this new type of composite anode material is that the construction of two stable interfaces between the active material and the buffer layer as well as interactions between the buffer layer and the binder through coordination and cross-link reaction are helpful to heighten the stability of the entire electrode system and thus prolong the electrode’s cycle life. By such a design, the reversible capacity was increased to 931 mA·h/g, corresponding to a CE of 68% for the polydopamine-coated rGO/SnO2 composite with crosslinking, as compared to the sample without cross-linking (800 mA·h/g, 57%) and bare rGO/SnO2 composite (520 mA·h/g, 40%) during the first cycle. More importantly, the polydopamine-coated RGO/SnO2 composite with cross-linking exhibited a far superior cyclic performance as compared to the sample without cross-linking and the bare rGO/SnO 2 composite with high capacity of 718 mA·h/g after 200 cycles at a density of 100 mA/g. Obviously, the covalent bond formed between polydopamine and PAA in polydopamine-coated rGO/SnO2 composite is far stronger than the van der Waals interaction and/or hydrogen bond between bare rGO/SnO2 composite and PAA, which can strengthen the interaction of individual components and greatly enhance the stability of the entire electrode system to withstand damage to its structure during cycling. 5.1.2. Dye-Sensitized Solar Cells. The development of metal-free and environmentally benign organic dyes with a broad absorption within the solar spectrum is a prerequisite for achieving highly efficient dye-sensitized solar cells (DSSCs) that hold great promise in future photovoltaic applications due to their high energy conversion efficiencies and low production cost.274 An ideal sensitizer must have a high molar extinction coefficient within the whole solar spectrum, which allows absorption of more solar energy by the sensitizer and leads to more efficient transfer of charge to the semiconductor film, thus largely increasing the energy conversion efficiency of the DSSCs. Encouragingly, the absorption of polydopamine can extend from UV light to near-infrared regions, which can significantly enhance light harvesting. Along with the excellent biocompatibility of polydopamine as well as its strong and robust binding ability to TiO2 (the semiconductor commonly used in DSSCs), these favorable properties confer great promise to polydopamine as an effective sensitizer for nextgeneration DSSCs. Recently, Jung and co-workers applied both dip-coating and electrochemical polymerization methods to prepare efficient polydopamine-based DSSCs (Figure 24).275 To control the polymerization rate and prevent the formation of polydopamine aggregates, the polymerization of dopamine on the TiO2 electrode surface was performed in N2-saturated tris(hydroxymethyl) aminomethane (THAM) buffer (pH 8.5) instead of the oxygen-containing buffer. The main absorber layer and the scattering layer were composed of TiO2 particles with mean diameters of 20 and 500 nm, respectively. The deposition of polydopamine occurred on both TiO2 layers to yield TiO2/polydopamine core/shell structures without any agglomerate. Different from conventional DSSCs in which the electron injection typically took place from the LUMO level of the dye to the conduction band (CB) of TiO2 through a two-

Figure 24. (A) Proposed schematic illustration of the photoinduced charge transfer process of polydopamine-sensitized solar cells. (B) High-resolution TEM images of polydopamine-coated 20 nm TiO2 electrodes by dip-coating. (C) Photocurrent density−voltage curves of the polydopamine-sensitized cells.275 Reprinted with permission from ref 275. Copyright 2012 Wiley-VCH.

step process under photoexcitation, the efficient electron injection for polydopamine-based DSSCs followed a one-step direct charge transfer process as catechol derivatives. In other words, the photon injected through the transparent conducting oxide layer was transferred from the HOMO energy level of polydopamine to CB of TiO2 nanoparticles upon photoexcitation. By optimizing the synthetic conditions, the maximum energy conversion efficiency η for polydopaminebased DSSCs via a dip-coating pathway was determined to be 1.2%, whereas it was decreased to 0.9% for polydopamine-based DSSCs via an electrochemical polymerization pathway due to the performance decrease of the FTO electrode caused by electrochemical oxidation. Although the η values for polydopamine-based DSSCs were much lower than those of conventional metal-containing inorganic dye-based DSSCs, some key issues of DSSCs in terms of their cost and environmental concern have been successfully addressed. 5.2. Supercapacitors

As compared to batteries, supercapacitors, also known as electrochemical capacitors or ultracapacitors, possess many properties that are currently unattainable for batteries involving higher power density, subsecond charging, ultralong cycle life, and a very wide range of operational temperature. Since their advent in the 1970s, they have found extensive practical applications that require rapid charging or large momentary current, such as in consumer electronics, energy management, memory back-up systems, industrial power ,and mobile electrical systems.276,277 Rational design of architectures on the basis of the properties of polydopamine has drawn from many polydopamine-derived hybrid materials for high-performance supercapacitors. The key role played by polydopamine in supercapacitors is to act as the carbon source for enhancing the conductivity of active materials. A typical example is the use of polydopamine as a building block and triblock copolymer PEO−PPO−PEO (P123) as the pore-forming agent to prepare one-dimensional manganese oxide/mesoporous carbon/man5085


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Figure 25. (A) Schematic image, (B) the formation procedure, (C) TEM image, and (D,E) the corresponding supercapacitive performances of Mn3O4/MC hybrid nanowires.278 Reprinted with permission from ref 278. Copyright 2011 Royal Society of Chemistry.

ganese oxide hybrid nanowires (Figure 25).278 This unique hybrid structure, when applied as electrode materials for supercapacitors, possesses several obvious merits. First, the high-level graphitic carbon and the presence of the heteroatom N in the outer mesoporous shells can overcome the poor conductivity of the manganese oxide. Second, the outer mesoporous carbon shells can facilitate the electron transfer and ions insertion/extraction, and also alleviate the possible volume expansion during cycling. Third, almost full utilization of the manganese oxide nanoparticles distributed on the surface of the mesoporous carbon layer for the improvement of capacitive performance can be realized due to their small size. Last but not least, the combination of the electrical double layer capacitance from the mesoporous carbon layer with the pseudocapacitance from metal oxide embedded inside can significantly enhance the specific capacitance of the whole system. Thanks to the synergetic effect of these factors, the specific capacitance of the obtained hybrid nanowires with optimal carbon content reached as high as 266 F/g at a current density of 1 A/g, which was approximately 1.7 times that of the pristine MnO2 nanowires. Even when the current density was increased to 60 A/g, the specific capacitance still remained at 150 F/g, corresponding to 56.4% of capacitance retention. Additionally, the hybrid nanowires also displayed a more stable cycle life over 1200 cycles, and the energy density could achieved up to 20.8 Wh/kg even at a high power density of 30 kW/kg. More specifically, this strategy can tackle the problems of conventional metal oxide/CNT composites with respect to the fabrication cost and the loading amount of metal oxide, which are central to the effects directed toward the ultimate practical applications. By means of a similar protocol, Ma and colleagues have also synthesized peapod-like metal Ni nanoparticles@mesoporous carbon core−shell nanowires, which also exhibited a high specific capacitance and rate capability that are superior or comparable to some of the best NiO/carbon composites previously reported in the literature with outstanding cycle stability.279 In addition to metal oxides, electroactive polymers represent another important choice of dielectric materials for energy

storage capacitors because of their many advantages over traditional electronic devices. Using electroactive polymers, the volume, weight, and cost of energy storage systems can be significantly reduced. Other potential advantages include solution processing, cost-effectiveness, large-scale manufacture, and higher charge storage capacity due to their higher breakdown strength. 280,281 However, one of the great challenges facing current researchers is the low dielectric constants of these polymers. Recently, Lee and co-workers noticed that the incorporation of polydopamine with these polymers could efficiently ameliorate the dielectric properties of these polymers.282 Fluoropolymers, poly(vinylidene fluoride) (PVDF), for example, have excellent mechanical strength and thermal stability, high volume resistivity, processability, and low shrinking rates, which in principle make them highly applicable for capacitors. Despite these favorable properties, the successful applications of these polymers in capacitors continue to be hampered by their low dielectric constant, chemical inertness, and hydrophobic nature. Moreover, they are very difficult to modify via purely chemical methods. Interestingly, electron beam irradiation-treated PVDF was easily coated with a polydopamine film. It was believed that dopamine interacted strongly with the peroxide and hydroperoxide species on the irradiated polymer backbone by hydrogen bonding and interactions between NH2 groups in dopamine and the OH groups in the irradiated polymer. The resultant PVDF− dopamine complex subsequently underwent polymerization of dopamine molecules on their surface to form a thin polydopamine film under basic conditions. By such an approach, the water-soluble functionalized PVDF was first successfully realized. The contact angle with water drastically declined from 98° to 57° by increasing the starting concentration of dopamine to 2.1 g/L. More importantly, the diol functionality and amine moiety that bridged the PVDF backbone and the polydopamine film enhanced the polarizability of the PVDF polymer, and a large amount of hydroxyl and amino groups incorporated in PVDF due to the polydopamine coating also contributes to a high dipole moment and polarizability. These two factors resulted in the 5086


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Figure 26. (A) EELS mapping analysis of polydopamine-based carbon submicrometer spheres. (B) Schematic illustration of chemical structure of PDA-based carbon submicrometer spheres. (C) CV plots of polydopamine(PDA)- and phenol/formaldehyde resin(PFR)-based carbon submicrometer spheres in N2- and O2-saturated 0.1 M KOH. (D) TEM image of Fe@Fe3C/C−N. (E) CV plots of Fe@Fe3C/C−N and the commercial 20 wt % Pt/C in N2- and O2-saturated 0.1 M KOH. (F) Polarization curves of 20 wt % Pt/C, Fe@Fe3C/C−N, Fe@Fe3C/C, PDA-, and PFR-based carbon SMSs in O2-saturated 0.5 M H2SO4.249 Reprinted with permission from ref 249. Copyright 2013 Wiley-VCH.

higher durability.283−285 It has been well demonstrated that the incorporation of heteroatom N or transitional metal-N into the carbon matrix can significantly enhance the number of active sites for improved ORR activity. Thus, numerous hybrid materials including transition metal-based materials, N-doped carbon materials, and metal−carbon hybrid materials have been investigated as catalysts or catalyst supports for ORR. Nevertheless, additional chemical pretreatments have been commonly required to introduce the nitrogen. In contrast, polydopamine intrinsically contains carbon and nitrogen atoms, as well as its well-know robust chelating capability with many types of transitional metal ions as discussed above. These favorable properties, in conjunction with its high chemical and thermal stability, make polydopamine ideal for in situ production of N-doped carbon/N-doped metal−carbon hybrid materials without the need for additional chemical pretreatments that are typically required in traditional nonprecious metal catalysts. The beneficial properties of polydopamine can effectively avoid the poor control over the reproducibility and chemical homogeneity, long preparation times, and deterioration of the structure of the target materials. However, the utilization of polydopamine as ORR electrocatalysts has rarely been achieved, possibly stemming from the short history of polydopamine and the lack of a full realization of its favorable properties. In 2012, Chen and co-workers prepared polydopaminederived hollow carbon microspheres using silica as the sacrificed template.286 The electrocatalytic activity of the asprepared hollow carbon microspheres for ORR was found to be higher than that of N-doped ordered mesoporous carbon reported elsewhere and comparable to that of the commercial

elevation of the dielectric constant of the PVDF polymer. On the other hand, the combination of crystalline PVDF with amorphous polydopamine can lead to the increase of free charge carriers in the amorphous phase and/or charge accumulation at the interface of different phases. As a result, the polydopamine-modified PVDF showed dielectric properties far superior to those of the pristine polymer. At 1 kHz, the dielectric constant of the polydopamine-modified PVDF was about 32, whereas the dielectric constant of the pristine PVDF was only 12 at the same frequency. Even at an extremely high frequency of 1 MHz, the polydopamine-modified PVDF could retain a higher dielectric constant than the pristine PVDF with only about 15% of dielectric loss, which makes polydopaminemodified PVDF very promising for applications in the field of high energy density capacitors. 5.3. Catalysts

5.3.1. Electrocatalysts. The oxygen reduction reaction (ORR) at the cathode plays a crucial role in controlling the performance of various renewable energy techniques, such as fuel cells, metal−air batteries, and chloralkali electrolysis. However, efficient electrocatalysts are necessary to enhance the kinetics of ORR due to the naturally sluggish progress of these reactions. To date, commercial ORR electrocatalysts have been limited to Pt-based materials, but their high cost, intolerance to fuel crossover, and decline in activity over time are still the greatest obstacles to the introduction of many renewable energy techniques to the large-scale market. Recently, intensive research efforts have been devoted to search for novel nonprecious metal ORR electrocatalysts with ORR catalytic activity higher than/comparable to that of the commercial Pt-based catalysts, but with much lower cost and 5087


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Figure 27. (A) Schematic illustration of synthetic procedure for nanograined CeO2 sheets. (B) SEM image of the nanograined CeO2 sheets. (C) UV−visible absorbance spectra of CeO2 sheets calcinated at different temperatures. (D,E) Photocatalytic degradation performance of nanograined CeO2 sheets toward methylene blue.295 Reprinted with permission from ref 295. Copyright 2013 Royal Society of Chemistry.

stance, by absorbing Fe3+ ions followed by carbonization, monodisperse Fe@Fe3C-loaded N-doped carbon (Fe@Fe3C/ C−N) spheres were obtained. The incorporation of iron enabled the further introduction of transitional metal-based electroactive substances and formed new active sites for ORR in the carbon matrix. As a result, the resultant Fe@Fe3C/C−N spheres showed significantly enhanced catalytic activity as compared to metal-free N-doped carbon spheres, and even displayed higher catalytic current than the commercial 20% Pt/ C catalyst but with excellent catalytic stability and selectivity (Figure 26). Apart from directly acting as the precursor of ORR electrocatalysts, polydopamine can also service as the building block for the construction of other kinds of electrocatalysts based on its remarkable degree of physicochemical versatility that has already inspired.287−289 Xin and co-workers found that in situ spontaneous oxidative polymerization of dopamine on CNTs could significantly increase the affinity of carbon nanotubes for water. Meanwhile, the polydopamine modification method can overcome some key issues with respect to traditional routes for the preparation of water-soluble CNTs; specific examples include multistep procedures, drastic reaction conditions, poor control over the coating thickness, breakdown of CNT sidewalls, low grafting density, and low reactivity, etc.287 In conjugation with the robust metal ion-chelating capability of polydopamine, Zhou and co-workers deposited Pd/Pt nanoparticles with high loading amount and good dispersivity on the surface of polydopamine-wrapped CNTs triggered by the reduction with NaBH4. Representative electrooxidation experiments of hydrazine and methanol prove that, as compared to the Pd/Pt decorated CNTs, the

Pt/C catalyst in the alkaline solution. The higher catalytic activity of the polydopamine-derived hollow carbon microspheres was mainly ascribed to their morphology that featured large dimension, hollow core, and porous thin shells, which could facilitate the transfer of oxygen as well as electrolytes and allow further exposure of active sites inside the catalyst to oxygen molecules. In addition, the polydopamine-derived hollow carbon microspheres also showed higher tolerance to the crossover effect of methanol and higher catalytic stability with approximately 16% of activity decay over 20 000 s of continuous operation as compared to the commercial Pt/C catalyst (48% of activity decay). In fact, without using any template, dopamine can selfpolymerize into polydopamine microspheres under alkaline solutions and yield N-doped carbon microspheres after carbonization as demonstrated in section 4.10. This procedure can efficiently avoid the use of highly toxic HF and simplify the preparation process. Very recently, Lu and co-workers prepared monodisperse size-controlled carbon microspheres through carbonization of polydopamine microspheres. Their ORR catalytic performance was systematically investigated.249 Different from traditional carbon microspheres produced via carbonization of phenol/formaldehyde resin, the polydopamine-derived carbon microspheres possessed high-level electroactive graphitic N and pyridinic N, which greatly increased the limiting current density and improved the onset potential. Another substantial benefit to this strategy is that many functional groups of polydopamine microspheres, such as catechol and N−H groups, inherited from the starting materials, can effectively absorb transitional metal ions to produce metal−nitrogen−carbon hybrid materials. For in5088


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mixtures, allowing recovery of the metal catalysts and preventing metal contamination of the product solutions.296 A major shortcoming of these supported-metal catalysts is their lower activities and selectivities when compared to their nonsupported analogues. The reasons are multifold and involve the density of the metal catalysts on the supported complexes, leaching of the metal, and the aggregation of metal catalysts during the course of a reaction. To overcome these problems, Demirel and co-workers have reported a simple but versatile method to develop supported-metal catalysts by coating them with polydopamine followed by electroless plating of the silver nanoparticles onto several kinds of nanomaterials (e.g., anodic aluminum oxide membranes and polystyrene nanotubes) for catalytic reduction.297 The strong metal ion-chelating and redox capability of polydopamine enabled a high density of Ag nanoparticles to be deposited on the supported materials without suffering from serious aggregation of Ag nanoparticles. A comparative study on the catalytic activities of the resultant supported-metal catalysts and unsupported Ag nanoparticles in the reduction of o-nitroaniline, one of the most refractory pollutants arising from the production of pesticides and synthetic dyes in industrial wastewaters, indicated that supported-metal catalysts exhibited significantly enhanced catalytic activities as compared to unsupported Ag nanoparticles. More importantly, the reuse and recovery of these catalysts is a facile process, which is a great advantage when considering the cost of these catalysts. Another effective strategy to solve the recycling problem associated with these noble metal-based catalysts is to endow them with strong magnetism through combination with magnetic materials, which can be removed from the products only by using an external magnetic field. It is well-known that the catechol groups in dopamine can strongly adhere to magnetic nanoparticles via the coordination interaction as demonstrated in section 3, and thus polydopamine can be an alternative medium for the manufacture of magnetic-noble metal catalysts without the need for the toxic reagents or heat treatments that are typically involved in traditional methods. Very recently, several research groups have reported magnetically recyclable nanocatalyst through in situ growth of Au nanoparticles onto presynthesized polydopamine-encapsulated Fe3O4 microspheres.298,299 The size and amount of Au nanoparticles were easily controlled by adjusting the concentration of the starting material (HAuCl4). The catalytic activity of the resultant Fe3O4@PDA−Au nanocomposites was examined in the reduction of o-nitroaniline and several nitrobenzene analogues to their corresponding daughter derivatives using sodium borohydride as the reducing agent. In the presence of a small amount of Fe3O4@PDA−Au composites, these compounds could be rapidly reduced, and the reactions monitored by UV−vis spectrometry were observed to be nearly completed after 7 min with a conversion up to 99%. More specifically, the catalyst could be reused after being separated from the reaction mixture by using an external magnet due to its high magnetization (39.6 emu/g). Besides, the catalyst still preserved a conversion of over 98% with no Fe and trace Au released after eight successive cycles, clearly demonstrating its excellent catalytic and chemical stability derived from the high reductive and stabilizing capacity of polydopamine layer.

Pd/Pt decorated CNTs@polydopamine composite demonstrated much higher electrocatalytic activity and longer stability.288 5.3.2. Photocatalysts and Chemical Catalysts. With rapid industrial development, large quantities of various toxic pollutants that are hazardous to human health have also been inevitably released into the environment. For instance, organic dyes and aromatic nitro compounds are two types of the most refractory pollutants resulting from the huge production of textiles as well as the manufacture of insecticides, pesticides, herbicides, and synthetic dyes every year. Most organic pollutants show high resistance to biodegradation, and Ncontaining dyes can yield potentially carcinogenic aromatic amines when undergoing naturally reductive anaerobic degradation.290−293 During recent decades, heterogeneous photocatalysis has been widely accepted as a cost-effective alternative for the practical purification of dye-containing wastewater. So far, various photocatalysts such as TiO2, ZnO, Ag, and AgPO4 nanoparticles have been developed for degradation of organic dyes, and they have shown many advances.291−293 While polydopamine has no photocatalytic capability for the degradation of organic dyes, it could have a synergistic effect with photocatalysts through the presence of the π−π* electron transition, which can largely improve the photocatalytic activity of the catalysts. Feng and co-workers synthesized monodisperse Ag@polydopamine core/shell nanoparticles based on the redox reaction of polydopamine toward Ag+ ions for the photocatalytic degradation of neutral red.294 Upon irradiation with UV light, the photodegradation rate of the dye was much faster with the Ag@polydopamine composite than by use of bare Ag nanoparticles, indicating the enhanced photocatalytic activity of the Ag@polydopamine. It is well-known that Ag nanoparticles can induce electrons and holes upon irradiation of UV light, and the photogenerated electrons and holes can be trapped by hydroxyl groups to produce the hydroxyl radical (·OH). On the other hand, the photogenerated electrons can also reduce the O2 molecules adsorbed on the surface of the catalyst, resulting in the formation of superoxide radicals (O2·−). These two types of reactive oxygen species can efficiently oxidize the neutral red dye due to their high oxidative activity. The polydopamine shell can not only adsorb more dye molecules onto the surface of the catalyst, but also can produce additional holes under the irradiation of UV light, leading to the prolonged recombination rate between the photoinduced electrons and holes. As a consequence, the cooperation between the Ag core and polydopamine shell greatly contributes to the enhanced photocatalytic efficiency of the dye degradation. Further, Park and co-workers employed polydopamine-assisted CaCO3 mineralization to synthesize visible light-active nanograined CeO2 sheets for dye degradation (Figure 27).295 The asprepared nanograined CeO2 sheets had narrowed bandgaps (2.71−2.83 eV), which facilitated the excitation of electrons from the valence band to the conduction band of the CeO2 sheets under visible light irradiation. Although these earlier studies improved catalytic activity, the recovery and recycling of these catalysts from the product solutions is hard to achieve in practical applications, which remains a concern with respect to the cost of these catalysts because the transition-metal resources are often scare and expensive. The immobilization of metal catalysts on a support, termed supported catalysis or “green catalysis”, is emerging as the most effective strategy to address this issue, as the supported complexes can be removed from the reaction 5089


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Figure 28. (A) Schematic representation of polydopamine encapsulation and surface functionalization of individual yeast cells. (B) TEM micrograph of polydopamine-encapsulated yeast cells. (C) Growth curve of native yeast cells (1), single polydopamine-coated yeast cells (2), and double polydopamine-coated yeast cells (3). (D) Survival of native yeast cells (1), single polydopamine-coated yeast cells (2), and double polydopaminecoated yeast cells (3) in the presence of lyticase.301 Reprinted with permission from ref 301. Copyright 2011 American Chemical Society.

6. APPLICATIONS IN BIOMEDICAL SCIENCE Biomedical applications represent one of the most important and widely investigated areas for the application of polydopamine-based materials. What makes this material particularly interesting in this field is that polydopamine not only displays outstanding biocompatibility and hydrophilicity, but also affords secondary reactions with a wide range of molecules, which provides an important platform for producing diverse hybrid materials with specific functionalities. In view of this, Städler and co-workers have published a review that focused on biomedical applications of polydopamine-derived materials.20 Thereafter, nevertheless, the favorable physicochemical versatility that polydopamine possesses has also stimulated, and is still leading to, an ever-growing number of biological and biomedical applications. Thus, this section will give an overview of past studies and will highlight recent investigations that involve the reasonable design and use of polydopamine-derived materials in the biological and biomedical fields.

living cells appears to be essential for these applications but has proved to be difficult and complicated to achieve.300 Recently, ever-growing works have tapped into the enormous potential of polydopamine in these fields, by showing successful immobilization of cells and biologically relevant substances on various substrates, as well as facile interaction of polydopamine with cell walls typically comprised of proteins with accessible amine and thiol moieties.301−309 For instance, Yang et al. proposed a biomimetic approach to the individual encapsulation of living yeast cells by coating them with a polydopamine layer, and immobilizing the cells on the substrate of choice after covalent functionalization of an avidin adlayer. The artificial polydopamine shell could control the cell division, while preserving these cells under harsh environments, such as attack by foreign substances (Figure 28).301 Spatial organization of cells on substrates, also denoted as cell patterning, was believed to be necessary for some specific applications such as biochips, tissue engineering scaffolds, etc.310−312 Achieving effective cell patterning should be guided by the following criteria: (i) The ink should be cost-effective and modified on the stamp via a simple fabrication procedures; (ii) the ink should be easily transferred from the stamp to various substrates and have high stability on the patterned substrates; and (iii) the ink on the substrates should have the

6.1. Cells Adhesion, Encapsulating, and Patterning

The direct utilization of living cells has led to the emergence of applications in many biomaterial research fields, such as cellbased devices, sensors, as well as studies with regard to cell−cell interactions and cell behaviors. Protection or immobilization of 5090


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ability to maintain long-term cell capture. From this perspective, the beneficial features of polydopamine come to mind and have been applied for patterning diverse cell lines through photolithography, microfluidic technique, and microcontact printing methods. Using polydopamine as the ink, several shortcomings of existing systems for cell patterning involving high cost, limitation to specific substrates, harsh handling conditions, and poor stability have been overcome. For instance, Park and co-workers were the first to utilize polydopamine as the ink for patterning of several cell lines, which have been widely used for the high-throughput screening of anticancer drugs, studies of bone tissue engineering and cell interaction, and cell-based devices, on the nonadhesive poly(dimethylsiloxane) (PDMS) substrate.313 These investigators found that the polydopamine adlayer remained very stable due to its durable adhesion capability even under harsh conditions (e.g., with organic solvents, strong acids, sonication, and heat treatment), and preserved long-term cell adherence. Moreover, such a cell adherence ability of polydopamine remained unchanged under extreme environments. Thereafter, Jiang and his colleagues successfully extended this method to other common laboratoryl materials including glass, polystyrene, and poly(dimethylsiloxane) in light of their previous report for patterning cells to investigate the relationship between areas of mammalian nuclei and that of the cells.314 The maximum time for confining cells in micropatterns could be prolonged to 26 days on polystyrene, and this method was also applicable for patterning bacteria, which may find applications in the fabrication of microbial microassays. Chien et al. further broadened this system to create functional micropatterns of cells in light of the secondary reactions of polydopamine; amine- or thiol-containing PEG, fluorescence-labeled protein, and metal nanoparticles have been readily immobilized on the micropatterns for potential biomedical or optical/electric applications (Figure 29).315 However, it must be mentioned here that not all types of cells can be successfully attached to the polydopamine coating. While PC12 cells, a neuronal cell line, can synthesize and secrete dopamine and possess dopamine receptors, polydopamine coating did not support their attachment, possibly due to the electrostatic repulsion between them. To address this problem, Tsai and co-workers reported some new insights on the design of stamps.316 Because many substances can be encapsulated in the polymer matrix during its formation process, the authors deposited specific molecules along with polydopamine on the stamps to assist the adhesion of those cells, which had weaker adhesion or failed to attach to polydopamine. PC12 cells and HepG2/C3A cells were selected as the models; by codeposition of poly(ethylene imine) (PEI) or PEI-g-galactose with polydopamine, both kinds of cells were found to be highly resistant to culture-induced detachment from the polydopamine-stamped substrates. By codeposition of nonfouling molecules such as PEG, this approach was further extended to cell patterning on cell-favorable substrates involving gold, glass, and TCPS substrates. Additionally, the polydopamine-stamped substrates possessed high stability against harsh conditions including acidic solution (0.1 N HCl), basic solution (0.1 N NaOH), detergent, and ultrasonication treatment for 1 h, which reflected the excellent stability of polydopamine as well.

Figure 29. (A) Schematic illustration of steps for cell patterning with polydopamine as the ink. (B) SEM image of the cell-patterned substrate. (C) Fluorescent microscopy image of the cell-patterned substrate after immobilization of FITC-BSA. Scale bar represents 100 μm.315 Reprinted with permission from ref 315. Copyright 2012 American Chemical Society.

6.2. Polydopamine Coating-Induced Toxicity Attenuation of Materials

In 2011, Hong et al. reported the first attempt at using polydopamine coating to decrease the toxicity of some functional materials.317 Semiconductor CdSe quantum dots (QDs) are well-known to their high quantum yields and good photostability, but a low concentration of CdSe QDs can trigger severe toxicity both in vitro and in vivo because of the release of hazards Cd+ and Se+ from the surface of quantum dots, which has become a significant barrier to the biological and medical applications, particularly to human trials.318 For instance, when exposed to blood plasma, these QDs have been proved to induce symptoms of pulmonary vascular thrombosis. Hong et al. investigated the in vivo toxicity of PEGencapsulated QDs with both anionic and cationic surface charges before and after polydopamine coating, as monitored by blood immunogenicity assay. Briefly, noncoated and polydopamine-coated QDs were, respectively, injected into two groups of Balb/C mice via the tail vein at a dose of 60 pmol/mouse. For comparison, the same volume of saline was also intravenously administrated into another group of mice. The blood was collected at 4 h postinjection for blood immunogenicity assay. Experimental results showed that the unmodified QDs showed a serious distortion effect on the leukocyte population, regardless of surface charges. The percentage of lymphocytes decreased from 74% (control group) to 59% and 52% for unmodified QDs with anionic and cationic surface charges, respectively. Conversely, after polydopamine coating, the percentage of lymphocytes remarkably increased to 68% for anionic QDs, and 71% for cationic QDs. Likewise, the neutrophil levels for polydopamine-coated QDs, an important indicator of the immune response, were all nearly equal to the control level, in marked contrast to 5091


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Figure 30. Antibacterial activities of polydopamine Ag/polydopamine/graphene nanocomposite toward Gram-negative bacteria E. coli cells (A and B) and Gram-positive bacteria B. subtilis (C and D) based on LB liquidmedium turbidity assays (A and C) and LB−agar plate tests (B and D).329 Reprinted with permission from ref 329. Copyright 2013 Royal Society of Chemistry.

polydopamine in enhancing tissue integration of implants with soft tissues. Polydopamine coating also has the ability to improve the cytocompatibility of carbon materials. For instance, the polydopamine coating has been clarified to be capable of increasing the water solubility of CNTs and providing a more suitable environment for cell growth as compared to unmodified CNTs.321,322 Very recently, Cheng et al. exploited the polymerization process to reduce graphene oxide and found that the resultant polydopamine-functionalized rGO possessed extremely superior blood compatibility as compared to GO.164 Numerous studies have implied that GO presented good performance in many applications such as drug delivery, imaging, photothermal therapy, etc. However, the hemolysis usually occurs with GO, because its amphiphilic structure and surfactant-like properties lead to strong interactions (electrostatic and hydrophobic interactions) between the GO and the lipid bilayer of the blood cell membrane. In the case of the polydopamine-modified rGO, on the other hand, the interaction between it and lipid bilayers was greatly suppressed, and the grafted polydopamine on the surface conferred stronger electrostatic repulsion between rGO and the lipid bilayers. As a result, the hemoglobin ratio decreased significantly from 78.5% to less than 1.8% at a concentration of 200 μg/mL.

evidently increased levels of the unmodified QDs. These results clearly revealed the attenuation effect of polydopamine on the intrinsic blood toxicity of semiconductor QDs. Further investigation indicated that polydopamine coating could also attenuate the inflammatory responses stimulated by implanted materials. Taking the biodegradable polymer poly(Llactic acid), for instance, the cage implants prepared from the biodegradable polymer poly(L-lactic acid) and polydopaminecoated poly(L-lactic acid) were separately implanted into the abdomens of SD-rats, and their early stage and late-stage in vivo inflammatory responses were respectively evaluated by the quantitative analysis of the number of macrophages present at 4 days after implantation and the number of foreign body giant cells at 14 days after implantation. The results showed that due to the hydrophobic nature of the surface, the poly(L-lactic acid) film stimulated a more significant inflammatory response, with 481.6 ± 31.3 macrophages and 13.8 ± 0.9 foreign body giant cells adhered to its surface. In contrast, less than two-fifths of the number of macrophages and approximately one-third as many foreign body giant cells were observed on the surface of the polydopamine-modified poly(L-lactic acid) film, which revealed the reduced inflammatory response. Apart from the attenuation of the inflammatory response of the implants, other studies further demonstrated that polydopamine could also improve the biointegration of implants with soft tissues.319,320 The authors chose poly(methyl methacrylate) (PMMA), a major material used in ophthalmology as a keratoprosthesis (KPro) optic, as the model surface. Pristine PMMA is generally inert and has poor adhesion to the surrounding tissues, which can provide a portal for bacteria and stimulate the bacterial infection in the globe. As illustrated, almost no corneal epithelial cells and a small amount of keratocytes survived on the pristine PMMA, which are two major corneal cell types that interact with the implants. On the other hand, polydopamine coating could enhance the survival of both types of cells without inducing excessive secretion of pro-inflammatory cytokines, which is useful for improvement of the material’s safety. After implantation in the dorsal lumbar subcutaneous tissue of rates, histological analysis indicated that polydopamine-coated PMMA adhered more tightly to the subcutaneous tissue than did the pristine PMMA, reflecting the critical role of

6.3. Antimicrobial Applications

Bacterial infections affect many critical fields such as medical, industry, food safety, and have led to serious threats to human health, even death. Nosocomial infection and bacterial fouling on different surfaces are believed to be a major cause of mortality. It was estimated that approximately 1.7 million hospitalized patients were afflicted by nosocomial infections in 2002, nearly one-half of which are device-related.323 Consequently, there is an urgent demand for effective antibacterial surfaces. In response, numerous antibacterial materials such as metallic nanoparticles (silver, copper, and gold) and semiconducting materials (TiO2 and ZnO) have been reported as antibacterial materials. Notwithstanding their high antibacterial activity, the question of how to apply these materials on different substrates remains a challenge. An effective solution is to develop coating materials that can strongly adhere to the substrates and simultaneously support the antibacterial 5092


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Figure 31. (A) Schematic drawing of antimicrobial and antifouling hydrogel coating on the silicone rubber surface. (B−D) Representative confocal images of attached S. aureus after exposure to the (B) silicone rubber surface, (C) PEG hydrogel-coated silicone rubber surface, and (D) quaternary ammonium salt containing gel-coated silicone rubber surface coated for 1 day. Live cells and dead cells are stained with a green fluorescent dye and a red fluorescent dye, respectively.332 Reprinted with permission from ref 332. Copyright 2012 Wiley-VCH.

nanofibrillar structure as the host system and polydopamine coating as both the reducing agent and the stabilizer for the silver nanoparticles. Magnetite was also incorporated into the polymer matrix to yield a magnetic silver nanocomposite.330 The as-obtained magnetic silver nanocomposite displayed an antibacterial activity against both gram-positive and -negative bacteria, and could be recovered by using an external magnetic field. To decrease the likelihood of bacterial resistance associated with leaching of silver, researchers have preferred to select antimicrobial polymers due to their broad-spectrum activities and ability to combat antibiotic-resistant microbes. Typically, Shalev et al. utilized the adhesion of polydopamine to modify surfaces of diverse materials with an antimicrobial peptide or quaternary ammonium salt.331 No leaching of the active antibacterial materials was observed. Polydopamine coating has also been used to anchor antimicrobial polycarbonateincorporated hydrogels on the silicone rubber to afford dual antifouling and antimicrobial functions (Figure 31).332 As compared to antimicrobial peptides, the resultant hydrogel coatings did not induce toxicity toward mammalian cells and skins in animal models, yet exhibited strong and broadspectrum antimicrobial activity against various pathogenic microbes and clinically relevant drug-resistant microbes. Very recently, Avis and co-workers found that polydopamine itself has intrinsic antimicrobial activity.333 Nevertheless, the antimicrobial mechanism is quite different from that of the Ag nanocomposite. When E. coli cells were coincubated with dopamine, they were encapsulated in the polydopamine shells with a thickness of 120 nm as indicated by UV and fluorescence spectroscopy, and the polydopamine shell could restrict the growth of bacterial cells and prevent their further multiplication. Alternatively, polydopamine shells may cause local toxic effects on the outer membrane of bacterial cells via creating a barrier with reduced permeability to specific components that are necessary to bacterial cell survival or preventing metabolic waste from releasing. Admittedly, the antibacterial activity of polydopamine was relatively weaker as compared to metal components. To improve the antibacterial

materials to resist bacterial attachment and proliferation, or kill the attached bacteria on the medical devices. Unfortunately, the lack of a simple and inexpensive coating approach has been the major obstacle for practical implementation, because substrates such as plastics, metals, and ceramics commonly have inert surfaces. The reducing capability of polydopamine toward metal ions as well as its robust adhesion on diverse substrates has been also employed for in situ fabrication of antimicrobial surfaces.324−328 In 2011, Messersmith’s group functionalized a polycarbonate substrate with polydopamine by an immersioncoating process. The polydopamine coating acted as a “primer”, onto which silver nanoparticles were deposited in situ followed by the grafting of the antifouling agent PEG. The resultant substrate could not only efficiently kill the clinically relevant gram-negative and gram-positive bacteria strains, but also hindered their attachment on the substrate.324 Considering the versatile coating ability of polydopamine, Mao and co-workers deposited polydopamine on the surfaces of cotton fabrics and used the polydopamine-modified cotton fabrics for in situ generation of silver nanoparticles to yield antibacterial cotton fabrics.325 Antibacterial activity assay against E. coli demonstrated that the bacteria could be completely killed by the antibacterial cotton fabrics. What is more, even after washing 30 times, the antibacterial cotton fabrics continued to reduce 99.99% of E. coli, which reflected their durable antibacterial activity and the robust stability of polydopamine as well. These striking results clearly suggested that polydopamine holds great promise for the fabrication of antibacterial bandages to prevent wound infections. Usually, silver nanoparticles as antibacterial materials have a strong tendency to aggregate and are easily oxidized. To enhance their stability, Tang and co-workers utilized polydopamine-modified graphene as the scaffold for in situ deposition of silver nanoparticles.329 The deposited silver nanoparticles were found to be uniformly distributed on the surface of polydopamine-modified graphene and could completely inhibit the growth of bacteria during the 48 h culture period at a low concentration of 1% (v/v) (Figure 30). Alternatively, Lee and his colleagues selected biocompatible cellulose with a 3D 5093


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occlusion of the dentin tubules by well-defined crystals and prevented the dentin surface from encountering external stimuli such as cold, thermal, acidic, or sweet, which may be a potential therapeutic technique for dentin hypersensitivity. Every year, millions of people suffer from the failure or loss of organs/tissues as a result of diseases or accidents. With the rapid development of technology in cellular and molecular biology, tissue engineering is expanding to fulfill people’s long sought dream with regard to the replacement of diseased or damaged parts of the human body with man-made organs or tissues without occurrence of disease transmission and recipient rejection.339 Research efforts toward tissue engineering have mainly concentrated on the development of effective scaffolds. In natural tissues, cell attachment, proliferation, and differentiation typically occur in the extracellular matrix (ECM). Thus, artificial scaffolds for tissue engineering should be analogous to the naturally occurring ECM in terms of the chemical composition and physical structure, which can provide a similar microenvironment for cell attachment, proliferation, and differentiation.340 Until now, artificial scaffolds have generally been highly porous and three-dimensional structures. Mesoporous materials such as SiO2 have been investigated as scaffolds for tissue engineering, because their large-pore structure offers a space for cell ingrowth and their mesopore structure is able to carry drugs that can stimulate bone-forming cells. Unfortunately, these mesoporous materials typically display poor cytocompatibility as well as a too slow mineralization rate. The facile and versatile surface modification technique based on strong adhesion of polydopamine has provided a new tool to address this issue. For instance, Xiao and co-workers modified porous SiO2 scaffolds with polydopamine and investigated the in vitro mineralization and proliferation of bone marrow stromal cells (BMSCs) on the polydopamine-modified SiO2 scaffolds.341 It was evident that with polydopamine coatings, the SiO2 scaffolds showed significant apatite mineralization after immersion in SBF, in marked contrast to untreated SiO2 scaffolds in which no obvious apatite mineralization was found after 3 days. Interestingly, the functionalization of polydopamine to SiO2 scaffolds did not induce any change in either the pore distribution of the mesopores or the drug release behavior. More importantly, significantly enhanced attachment and proliferation of BMSCs on the polydopamine-modified SiO2 scaffolds were observed. The enhancement mechanism involves three functions of polydopamine. The first one is its strong adhesion, which can strengthen the interaction between cells and the scaffold. The fact that polydopamine can improve the hydrophilicity of the scaffold should be taken into consideration as the second factor for facilitating the attachment and proliferation of BMSCs. The third factor is that polydopamine-promoted apatite mineralization is capable of enhancing osteoblastic activity and thereby stimulating the cell proliferation and differentiation. Despite these achievements, it is fair to admit there is still a concern regarding the biodegradation of the scaffolds, because SiO2 is an inert material in vivo. In comparison, biodegradable polymers such as poly-L-lactic acid (PLGA) and polyurethane (PU) are popular materials for the fabrication of artificial scaffolds, because of their many merits involving controllable degradation, good processability, and high reproducibility. Likewise, the cell affinity on these synthetic scaffolds is also far from optimal, and how to enhance their cell affinity as well as promote cell proliferation and differentiation on these polymers has become a key focus in

activity, Rahimipour and co-workers explored polydopamine capsules prepared by sonochemical method in the presence of the oxidizing agent CuSO4, and studied their antibacterial performance.242 Because of chelating of Cu(II), polydopamine capsules could selectively kill S. aureus, S. mutans, and P. aeruginosa with high efficiency; 99.9% of bacterial cells were killed when 3.3 g/mL CuSO4 was presented during the synthesis progress, in contrast to 20% of bacterial killing with Cu-free polydopamine capsules. 6.4. Tooth Remineralization and Tissue Engineering

As a noninvasive therapeutic technique, tooth remineralization has been gradually accepted in recent decades in clinical dentistry. Currently, commercially available remineralization materials mainly focus on calcium phosphate-based materials including casein phosphopeptide-stabilized amorphous calcium phosphate, unstabilized amorphous calcium phosphate, and a bioactive glass containing calcium sodium phosphosilicate.334,335 Although these remineralization materials can efficiently realize the remineralization of enamel, they are not capable of remineralizing the fully demineralized dentin. This is mainly attributed to differences in the remineralization mechanisms between enamel and dentin. The main unit of enamel is tightly packed fibril-like carbonate hydroxyapatite crystals, and enamel demineralization would lead to the exposure of fresh carbonate hydroxyapatite crystals. Conversely, dentin consists of dentinal tubules surrounded by dense peritubular dentin, and the dense peritubular dentin comprises mineralized collagen fibrils. Thus, acid-etching of dentin would induce exposure of collagen matrix.336 The remineralization of enamel is a result of epitaxial growth progress of carbonate hydroxyapatite crystals in the presence of apatite seed crystallites.337 However, the nucleation and in situ regeneration of carbonate hydroxyapatite crystals on the exposed collagen matrix in demineralized dentin is much more difficult. A feasible solution to this problem is to search for effective scaffolds that can anchor to the natural organic matrices, and also mimic the role of natural organic matrices for ingrowth of carbonate hydroxyapatite crystals on the surface of dentin. In section 2, we described that polydopamine can induce mineralization of hydroxyapatites, and this phenomenon, in combination with robust adhesion of polydopamine, may allow polydopamine to be used as the scaffolds for the remineralization of the demineralized dentin. This hypothesis has been illustrated by a recent study carried out on human molars. Employing SEM analysis, Li and co-workers showed clear evidence that polydopamine could be successfully coated onto the collagen fibers of demineralized dentin in a film-like form.338 Following 2 days of the remineralization procedure, dispersed carbonate hydroxyapatite crystals were observed to be evenly distributed on the surface of polydopamine-coated dentin as well as at the interior of dentin tubules. Conversely, few carbonate hydroxyapatite crystals could be found on the surface of uncoated dentin and in the dentin tubules over this time period. These results indicated that catecholamine moieties of polydopamine bound to Ca2+ ions and presented new nucleation sites for the growth of carbonate hydroxyapatite crystals. The hardness of the regenerated carbonate hydroxyapatite crystals was then evaluated by a Tukey’s test. Although the hardness value of the regenerated carbonate hydroxyapatite crystals (50.7 ± 10.1) did not reach the value of intact dentin (58.7 ± 6.0), it was much higher than that of the acid-etching dentin (44.7 ± 9.3). Besides, polydopamine coating allowed 5094


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Figure 32. (A) Schematic illustration of cell adhesion on polydopamine-coated polycaprolactone nanofibers. (B) SEM images of unmodified and polydopamine-coated polycaprolactone nanofibers. (C) Water contact angle measurement of unmodified and polydopamine-coated polycaprolactone nanofibers. (D) Cell morphology, (E) the number of live cells, and (F) fold-increase of cell viability for HUVECs grown on unmodified, gelatin-coated, and polydopamine-coated polycaprolactone nanofibers.342 Reprinted with permission from ref 342. Copyright 2010 Elsevier.

tissue engineering. In an effort to improve the cell affinity of these polymers, Park and co-workers deposited a thin polydopamine layer on the biodegradable polycaprolactone (PCL) nanofibers.342 The effect of polydopamine coating on cell attachment and viability has been well illustrated by a study carried out by culturing human umbilical vein endothelial cells on unmodified and polydopamine-modified nanofibers. As shown in Figure 32, the cells could attach, spread, and survive better on polydopamine-modified PCL nanofibers in comparison to both unmodified and gelatin-coated nanofibers. MTT assay verified that human umbilical vein endothelial cells showed an almost 5-fold increase in viability on polydopaminemodified nanofibers, indicating that polydopamine was highly effective for the enhancement of cell adhesion and viability on the scaffolds, and its effect was even higher than that of gelatin, which has been widely used for cell adhesion. Similar enhancement effects of polydopamine coating on the adhesion and proliferation were also observed on other types of biodegradable polymers. Tsai et al. found that after 5 min of polydopamine deposition, rabbit chondrocytes could adhere to and fully spread on polydopamine-modified PLGA, PU, polycaprolactone, and poly(lactic-co-glycolic acid), with a

1.35−2.69-fold increase of the cell adhesion as compared to untreated polymers.343 Immobilization of bioactive molecules onto scaffolds has been accepted as an efficient route for manipulation of neural stem cell behavior, which is a key process in cell therapies and tissue engineering. The facile and versatile polydopaminemediated functionalization of the polymer surface has also been successfully employed to manipulate stem cell behavior.344,345 In this case, polydopamine was anchored on the surface of scaffolds through noncovalent binding and then conjugated to bioactive molecules via Michael addition and/or Schiff base reaction. For example, amine- and thiol-containing growth factors and adhesion peptides were immobilized on the polydopamine-coated PS and PLGA scaffolds, and the resultant scaffolds were observed to be effective for neuronal differentiation and proliferation of both human and mouse fetal neural stem cells. All of the above results clearly imply that polydopamine-mediated surface modification techniques can offer a versatile platform for developing chemically defined and safe scaffolds for tissue engineering. Nevertheless, the development of polydopamine in tissue engineering is still at a very early stage, and further in vivo investigations are still required. 5095


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Figure 33. (A) SEM image of polydopamine colloidal nanoparticles. (B) Temperature elevation of water and polydopamine colloidal nanoparticle aqueous solutions with different concentrations as a function of irradiation time (800 nm, 2 W/cm2). (C) Cell viability of 4T1 cells treated with different concentrations of polydopamine colloidal nanoparticles and laser irradiation (808 nm, 2 W/cm2, 5 min). (D) In vivo MR images of the 4T1 tumor-bearing mouse before and after intravenous injection of the Gd-DTPA-modified polydopamine colloidal nanoparticle solution. The red circles point to the tumor sites. (E) Digital photos of the 4T1 tumor-bearing mouse before and after photothermal therapy.104 Reprinted with permission from ref 104. Copyright 2013 Wiley-VCH.

times higher than that on gelatin-modified nanofibers.342 A further study carried out by Yang et al. has given a more detailed evaluation about the feasibility of polydopamine as a multifunctional interface material for vascular devices. The biocompatibility, hemocompatibility, stability, and mechanical behavior of the polydopamine-coated 316L SS stents have been assessed in great detail.348 The polydopamine coating on the 316L SS stent was flexible without suffering from cracking or peeling from the stent during the balloon expansion test. After 1 day’s culture, the ratios of vital human umbilical vein endothelial cells on polydopamine-coated stents increased to 88.6% as compared to the control stent (58.8%), indicating the rapid re-endothelialization. Excitingly, SCMs were observed to be more isolated on the polydopamine-coated 316L SS stent than on the control 316L SS stent. As culture time proceeded, almost no proliferation of SCMs on the polydopamine-coated 316L SS stent was detected, whereas the number of SCMs on the control 316L SS stent showed a rapid increase. On the basis of the data obtained in this study, polydopamine may provide physicians with important new tools for the treatment of coronary artery disease with minimum complications.

6.5. Re-endothelialization of Vascular Devices

Vascular stents represent one of the most common strategies for treating severe coronary artery disease, which is a leading cause of death in the world. To reduce the possibility of in-sent restenosis, a major complication after implantation of vascular stents, drug-eluting stent systems have been developed as they can dramatically blunt the proliferation of vascular smooth muscle cells (VSMCs). These systems, nevertheless, have also been proved to inhibit endothelial cell (EC) adhesion, migration, and proliferation on the surface of vascular stents, resulting in poor re-endothelialization of vascular stents and a subsequent serious thrombosis.346,347 To minimize complications, it is highly desirable to develop novel vascular stents that can promote adhesion, migration, and proliferation of ECs, while inhibiting the proliferation of VSMCs in the wall. Surface modification of vascular stents with bioactive materials that can support the attachment and proliferation of ECs may be an effective route. Although the problem associated with EC adhesion and growth has been solved, currently exploited coating materials have failed to efficiently inhibit SMS proliferation, and may even stimulate this process. The aforementioned effects of polydopamine coating in enhancing cell adhesion and viability also pushed researchers to examine its potential in re-endothelialization of vascular devices. Ku et al. found that human umbilical vein endothelial cells could attach and spread better on polydopamine-modified polycaprolactone nanofibers in comparison to unmodified or gelatin-coated polycaprolactone nanofibers. The number of live cells on polydopamine-modified nanofibers was nearly 3 times higher than that on unmodified nanofibers, and more than 2

6.6. In Vivo Cancer Diagnosis and Photothermal Therapy

The near-infrared (NIR) optical window is related to a range of wavelengths (700−1300 nm) in which biological tissues have very low absorption. Further, the NIR has much deeper tissue penetration depth as compared to either visible light or UV light. As a consequence, biologically relevant imaging and therapy modalities commonly employ light at these wavelengths to monitor and trigger biological events both in vitro 5096


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and in vivo.349 For instance, photothermal therapy makes use of photosensitizing agents for absorbing the NIR and subsequently transducing the absorbed light into heat. The generated thermal energy can be used for destroying the cancer cells. Because of its high selectivity and minimal invasiveness, photothermal therapy is emerging as a potential substitute treatment approach for current clinical cancer therapies including surgery, radiotherapy, and chemotherapy.350 Definitely different from the traditional clinical cancer therapies, the therapeutic effect of photothermal therapy occurs only at the tumor sites with both photosensitizing agent accumulation and localized NIR laser exposure. Thus, this technique can effective avoid the risks associated with using clinical cancer therapies, such as killing normal cells, destroying the immune system, and an increased incidence of secondary cancers. Despite the intense interest in NIR photothermal therapeutic agents, there are still considerable challenges to overcome on the way to clinical implementation. The biggest one lies in the long term safety in vivo of these therapeutic agents. In 2013, Messersmith’s group employed polydopaminecoated Au nanorods as the photothermal therapeutic agent, and good in vitro therapeutic effects were obtained.351 Indeed, the strong absorption of polydopamine in the NIR region, in combination with its excellent biocompatibility, makes polydopamine very attractive as a new generation of photothermal therapeutic agents to overcome these issues with respect to the currently available photothermal therapeutic agents. Inspired by this, Lu’s group recently presented for the first time a novel photothermal therapeutic agent based on polydopamine colloidal nanospheres denoted hereafter as Dpamelanin CNSs for in vivo cancer therapy (Figure 33).104 The resultant Dpa-melanin CNSs displayed favorable colloidal stability in water without any detectable agglomeration even after several months. Upon irradiation with an 808 nm laser at a power density of 2 W/cm2, the temperature of the Dpa-melanin CNSs aqueous solution rapidly increased, rising by 33.6 °C after 500 s of laser irradiation at a concentration of 200 μg/mL, which was high enough to kill the cancer cells. Because of the excellent photostability and negligible resonance light scattering, the photothermal conversion efficiency of Dpa-melanin CNSs was as high as 40%, much higher than that of Au nanorods, which have been widely investigated for cancer therapy. In vitro photothermal cytotoxicity measurements illustrated that the cancer cells treated with both Dpa-melanin CNSs and laser irradiation were effectively killed, whereas cells treated with either laser alone or Dpa-melanin CNSs remained alive, which further revealed the safety of this technique. To assess the feasibility of Dpa-melanin CNSs for in vivo cancer therapy, an aqueous solution of Dpa-melanin CNSs was administrated intratumorally into 4T1 tumor-bearing mice. Following exposure to an 808 nm laser at 2 W/cm 2 for 5 min, the tumor size was monitored every other day for 10 days. The results demonstrated that after treatment with both Dpamelanin CNSs and laser irradiation, the tumors were all ablated with no regrowth phenomenon observed. More specifically, the postmodification of conjugates with other interesting biofunctionalities on the surfaces of Dpa-melanin CNSs could be easily achieved on the basis of the Michael addition and/or Schiff base reaction. For example, Gd-DTPA was successfully attached to their surface using biamino-terminated polyethylene glycol as the cross-linker. Following intravenous administration, the Gd-DTPA-functionalized Dpa-melanin CNSs could grad-

ually and passively accumulate in the tumor as verified by magnetic resonance imaging (MRI). After laser irradiation, the tumor was also damaged, which allowed the simultaneous diagnosis and therapy for the cancer (i.e., the term “theranostic” has been developed to describe these agents). More recently, Stritzker et al. proposed novel “stand-alone” theranostic agents through the insertion of reporter genes in melanogenesis to oncolytic viruses.352 Oncolytic viruses are a class of virus that have weak pathogenicity but that preferentially infect tumor cells or selectively replicate in tumor cells. They can destroy cancer cells through lysis and release new infectious virus particles to help destroy the remaining tumor. In that study, cDNAs of the key enzymes in melanogenesis were inserted into the vaccinia virus and could drive the overproduction of melanin in the vaccinia virus strain GLV-1h68, as verified by the color change in the cell pellet and skins of the injected mice. The produced melanin, especially eumelanin, was known to have efficient binding capacity for iron ions, which served as an excellent reporter for MRI. The temperature of the melanin-rVACV cell suspension was increased by 41 °C during 2 min of exposure to the laser light. The in vivo tumor therapeutic effect was investigated by monitoring the tumor size weekly after injection of melaninrVACV cell suspension. Because of the combination of photothermal therapy with oncolytic virotherapy, the tumor tissue was damaged and the tumor growth could be significantly restricted, whearas rapid tumor growth was observed in the control group. Besides, the yielded heat could be further converted into ultrasound signals that allowed for highresolution optoacoustic imaging. Thus, multimodel imaging and enhanced tumor-target killing efficiency have been achieved. 6.7. Bioimaging

As depicted in section 2, the polydopamine materials autofluoresce with peak emission at 400−550 nm. Together with their fine biocompatibility, these superior reagents distinguish themselves from traditional fluorescent materials such as semiconductor quantum dots and organic dyes, making polydopamine materials promising candidates for bioimaging and medical diagnosis. Despite these strong points, unfortunately, the fluorescence intensity of polydopamine materials appears too weak to be used for applications in fluorescence imaging. Recently, Wei and co-workers have reported polydopamine fluorescent organic nanoparticles with enhanced fluorescence.353 Polydopamine nanoparticles were first produced by self-polymerization of dopamine in an alkaline solution (pH 10.5). Subsequently, the resultant polydopamine nanoparticles were oxidized by H2O2 for 5 h to yield the polydopamine fluorescent organic nanoparticles. Bright blue fluorescence was observed when the suspension of these nanoparticles was irradiated by a 365 nm UV lamp, and the emission spectrum of these nanoparticles was broad, ranging from 470 (blue) to 550 nm (green), with a dependence on the excitation wavelengths due to the wide size distribution of these nanoparticles. Their fluorescence intensity reached a maximum at 440 nm excitation. It is worth noting that these polydopamine fluorescent organic nanoparticles possess remarkable photostability without suffering from detectable photobleaching during continuous excitation at 365 nm for 30 min, which is a crucial factor in determining their suitability for bioimaging applications. During incubation with NIH-3T3 cells, these nanoparticles could be internalized by the cells without 5097


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isoelectric point of polydopamine, the walls of the polydopamine capsules were positively charged. However, at the same pH, the MO molecule is in the neutral state but with an anionic sulfonate group, and alizarin red carries negative charges. Therefore, the positively charged polydopamine capsules displayed a high payload for MO/alizarin red molecules based on electrostatic interaction between them. On the other hand, there was a strong repulsive force between polydopamine capsules and Rh6G molecules, because Rh6G is protonated at this pH value, resulting in almost no loading of Rh6G molecules in polydopamine capsules. At a higher pH value (pH 8.5), nevertheless, the loading behavior of polydopamine capsules was reversed, that is, a high payload of Rh6G while no loading of MO and alizarin red occurred. This is because at pH 8.5, the deprotonation of the phenolic groups endowed the polydopamine capsules with negatively charged walls. Taking advantage of the different charged states of polydopamine capsules, the control over the selective loading of certain drugs can be expected. Very recently, Wang and coworkers reported pH and temperature dual-responsive capsules by grafting random copolymer brushes of 2-(2methoxyethoxy)ethyl methacrylate and oligo(ethylene glycol) methacrylate on the surfaces of polydopamine capsules. The resulting capsules exhibited controllable loading and release with respect to Rh6G (MO) by changes in the pH values and temperature of the solution.357 Despite the highly selective loading behavior, to some extent, the above system still encounters unsatisfactory drug release in the aqueous media. To overcome this problem, Caruso and coworkers developed a novel stimuli-responsive drug delivery system by covalently functionalizing the surfaces of polydopamine capsules with a pH-cleavable poly(methacrylic acid) (PMASH)-doxorubicin (Dox, an anticancer drug) conjugate.358 The resultant drug delivery system was highly soluble and stable in aqueous and buffer solution with the Dox release below 20% under the physiological pH conditions over a 12 h period. When the pH value was decreased, an elevated Dox release was observed, and approximately 85% of the drug was released at pH 5.0 over the same period of time. In vitro assays showed that Dox-loaded polydopamine capsules were more effective than free Dox in terms of killing the HeLa cells at the same concentrations of Dox. With this drug delivery system, enhanced in vivo therapeutic efficiency and reduced systemic toxicity of free drugs may be achieved.

hindering the cell viability, and the cells emitted green and green−yellow fluorescence upon excitation by a laser at 405 and 458 nm, respectively. A detailed investigation of the fluorescence enhancement mechanism has not been performed, but it is believed that the oxidation of H2O2 changed the structure or composition of polydopamine nanoparticles, because polydopamine is sensitive to H2O2 according to the literature and the absorption band of the H2O2-oxidized polydopamine nanoparticles was observed to be different from the initial polydopamine materials as reported previously. Apart from acting as a fluorescent material, polydopamine has been recently proved to improve the optical properties of some fluorescent materials, which is greatly beneficial for bioimaging.354−356 For instance, Lee and co-workers found that after coating with polydopamine, the photoluminescent intensity of graphene quantum dots (GQDs) could be well retained for 14 days in diverse buffers with acid, neutral, and base pH conditions, whearas noncoated GQDs lost 45% of initial photoluminescent intensity after 14 days of incubation in PBS buffer. It was explained that polydopamine coating could protect GQDs from aggregation or protonation, leading to the enhancement of photoluminescent stability. More importantly, the polydopamine coating increased dramatically the biocompatibility of GQDs. After administration into the mice, polydopamine-coated GQDs showed long-term and more stable luminescent signals in organs as compared to noncoated GQDs.354 In another paper, Zhu and co-workers reported a novel fluorescent/magnetic nanoprobe using polydopamine as the interlayer. The polydopamine interlayer could not only prevent the quenching effect of the CdSeTe@ZnS core but also offer a versatile platform for the conjungation of aptamer. This nanoprobe was successfully used for targeted multimodal cell imaging and on-chip sorting.355 6.8. Drug Delivery

Polydopamine capsules have been proposed as a good material for drug delivery, not only because of their high water solubility, excellent biocompatibility, and biodegradation, but also because of their cavities as well as their surfaces that allow high payloads of drug molecules. As described in section 2, hydrophobic anticancer drugs can be readily encapsulated in the cavities of the polydopamine capsules through preloading them in the emulsion template, and the drugs are retained in the capsules after the removal of the template. In contrast with this report, Zhou and co-worker have found that the as-prepared polydopamine capsules could also take up drugs on the basis of the tunable charged states of polydopamine.113 The drug loading behavior of the as-prepared polydopamine capsules was evaluated using rhodamine 6G (Rh6G) as the drug model and the probe. The loading of Rh6G occurred not only at the walls of polydopamine capsules but also at their interiors as confirmed by fluorescence microscopy, and the loading of Rh6G increased as the size of the capsule increased due to the enlarged interior volume. Further investigation showed that the loading behavior of polydopamine microcapsules was highly dependent on the pH value of the solution as well as the charge character of the loading molecules.236 In detail, Rh6G, methyl orange (MO), and alizarin red with cationic or anionic natures at different pH values were selected as the model molecules. It has been demonstrated that polydopamine exhibited zwitterionicity because of the presence of different functional groups. At a lower pH value (pH 3.0), which is lower than the

7. APPLICATIONS IN WATER TREATMENT 7.1. Separation of Heavy Metal, Organic Pollutants, and Bacteria from Water

With the growing demand for the removal of industrial pollutants such as heavy metals, synthetic dyes, and aromatic pollutants from water because of their threat to the environment and human health, tremendous efforts have been devoted to searching for highly effective water-purification methods.359,360 In addition to photocatalytic degradation as mentioned above, other methods including chemical precipitation, adsorption, biological treatment, and membrane filtration are also being explored in industry to remove these contaminants. Among these methods, adsorption has proved to be the most efficient and widely used strategy due to its easy operation, low cost, and fewer toxic byproducts. For achieving a high adsorption rate, the adsorbents are required to have a large number of binding sites for these contaminants. Taking into 5098


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Figure 34. (A) Photograph of GO dispersion and PDA-modified graphene hydrogel. (B) SEM image of the PDA-modified graphene hydrogel. (C− F) A comparison of adsorption behaviors of PDA-modified graphene hydrogel with hydrothermally synthesized graphene hydrogel todward Pb(II) and Cd(II).365 Reprinted with permission from ref 365. Copyright 2013 American Chemical Society.

particles with an electrokinetic injection time of 48 s.363 The low bonding affinity toward naphthalene acetic acid was attributed to the weak interaction between the amino/imino/ catechol groups in polydopamine and the carboxyl groups in naphthalene acetic acid. More interestingly, due to the strong adhesion of polydopamine, E. coli bacterium was nearly completely seized by polydopamine-modified magnetic nanoparticles, suggesting a potential technology for practical wastewater treatment and food safety. Similar results were also obtained by using capillary electrophoresis analysis. Besides the aforementioned active sites, a high surface area is also a crucial factor for adsorbent materials. Carbon-based nanomaterials, especially graphene, have been investigated as adsorbent materials for removal of heavy metals and organic contaminations due to their extremely high specific surface area. Nevertheless, the adsorption efficiency of these carbon nanomaterials is still significantly limited by their relatively low amount of functional groups.364 Once the high surface area of these carbon nanomaterials is combined with high-level active sites of polydopamine, a high adsorption capacity and efficiency can be anticipated. On this basis, Duan and coworkers reported a polydopamine-modified graphene hydrogel for wastewater treatment.365 By heating a mixture containing dopamine and graphene oxides at 60 °C for 6 h without any disturbance, a free-standing black cylinder corresponding to polydopamine-modified graphene hydrogel appeared at the bottom of the glass vessel. With this facile procedure, graphene nanosheets can self-assemble into a three-dimension porous structure with polydopamine uniformly coated on the basal planes of graphene due to the strong affinity of aromatic rings of polydopamine and graphene nanosheets. The specific surface area of the resultant hydrogel was measured to be 310.6 m2/g. Adsorption experiments were carried out with the graphene hydrogel prepared by the hydrothermal method as a reference. Because of larger amounts of binding sites, the maximum adsorption capacities of the polydopamine-modified graphene hydrogel toward Pb(II) at pH 6 and Cd(II) were 336.32 and 145.48 mg/g (Figure 34), respectively, which were about 3 and 1.4 times those for the pristine graphene hydrogel, respectively,

consideration the existence of abundant functional groups such as catechol groups, amine groups, and aromatic moieties, polydopamine is expected to offer a large number of active sites for binding heavy metal ions and organic pollutants via electrostatic interaction, coordination or chelation, hydrogen bonding, or π−π stacking interactions, which has stimulated extensive research on the polydopamine-based adsorbent materials. A typical example is the direct use of polydopamine nanoparticles as an adsorbent for copper ions in water reported by Farhadi’s group.361 Copper is an essential trace element in the human body and has multiple distinct functions, but excessive intake of copper will induce many serious neurodegenerative diseases, such as Menkes disease, Wilson disease, and Alzheimer’s disease.362 As stated above, copper ions are not only able to catalyze the polymerization of dopamine, but they can also bind to the resultant polydopamine through coordination interactions, which, in turn, makes polydopamine a potential adsorbent material for the removal of copper ions in water. The adsorption ability of copper ions was observed to be highly dependent on solution pH. At a pH value below 2, the structure of polydopamine was completely destroyed, whereas higher pH (over 5) will cause the formation of copper hydroxide and thereby decrease the adsorption. The maximum adsorption capacity of copper ions was found to be 34.4 mg/g at pH 5 within 270 min. To some extent, however, the adsorption capacity of polydopamine nanoparticles is too low and hence cannot be incorporated into practical applications, possibly stemming from their low surface area. In the adsorption applications, magnetic materials have aroused great interest as they can efficiently collect hazardous substances in water by using a magnetic field, thus avoiding the occurrence of secondary pollution of water due to the residual absorbents. In 2011, Lai and co-workers explored capillary electrophoresis and UV to investigate the binding kinetics of polydopamine-modified magnetic nanoparticles to several hazardous compounds, and found 97% of proflavine, 90% of bisphenol A, and 20% of naphthalene acetic acid could be rapidly bound on the polydopamine-modified magnetic nano5099


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Figure 35. (A) Synthetic scheme of the synthesis of superhydrophobic particles. (B−D) SEM images of SiO2, polydopamine-coated SiO2, and Ag NPs/polydopamine/SiO2 particles, respectively. (E) Image of a water droplet sitting on the superhydrophobic particles composed surface. (F) Water/oil separation of magnetic superhydrophobic particles prepared via a similar method with carbonyl iron particles as the core material. (G) The as-formed “oil marble” under water.368 Reprinted with permission from ref 368. Copyright 2012 American Chemical Society.

natural absorbers such as activated carbon is widely used in industry. However, these conventional materials have low oil loading and absorption of water together with the oil.367 Numerous efforts have been made to construct diverse superhydrophobic materials with a high oil-absorption ratio to address these problems. The use of polydopamine for the fabrication of superhydrophobic materials typically relies on its versatile adhesion and ease of functionalization, which facilitates the formation of hybrid materials with low surface energy. Xu and co-workers reported a general strategy to generate core/ shell/satellite composite particles with a hierarchical structure similar to the micromorphology of the lotus leaf as illustrated in Figure 35.368 The resultant polydopamine-based superhydrophobic materials have high performance in oil absorption. As shown in Figure 35, a drop of red dye containing oil was dropped into the water, and subsequent addition of magnetic superhydrophobic nanoparticles led to the complete absorption of oil. These nanoparticles showed an oil absorption ratio of 2 g oil/g particles and could be recycled after washing and filtration with superhydrophobicity intact. More interestingly, the magnetic superhydrophobic nanoparticles could drive the oil when a magnet approached, indicating the potential of these particles in controllable oil isolation. In parallel with this study, an oil/water separation mesh has been successfully developed by modification of stainless steel mesh with polydopamine, followed by conjugation of n-dodecyl mercaptan.369 The resulting mesh showed high hydrophobicity with the water contact angle of 144°, and was able to separate a series of oil/ water mixtures like gasoline, diesel, etc. The separation efficiency remained high even after 30 times use (99.95% for hexane/water mixture). Additionally, Cheng and his colleagues prepared GO-based aerogel via self-polydopamine-coated rGO nanosheets as the building block. The resulting GO-based aerogel exhibited not only high hydrophobicity but also high porosity, which allowed GO-based aerogel to be used as an adsorbent for oil/water separation with an excellent regeneration capacity.370

and also superior to many previously reported graphene and CNT-based adsorbents. Furthermore, the polydopaminemodified graphene hydrogel also possessed much higher adsorption capacity toward rhodamine B than the pristine graphene hydrogel at pH 6−7. The enhanced adsorption capacity toward these two heavy metal ions and rhodamine B was mainly ascribed to the strong electrostatic interactions between the polydopamine-modified graphene hydrogel and these pollutants, because the surface of the adsorbent is negatively charged due to the ionization of oxygen functional groups. However, its adsorption capacity for some other pollutants dominated by π−π stacking interactions, such as pnitrophenol, was observed to be a little lower than that of the pristine graphene hydrogel, possibly arising from the polydopamine modification-induced decrease of π−π stacking interactions between the aromatic ring of p-nitrophenol and the graphitic backbone of the graphene hydrogel. Considering the abundance, low cost, and high specific surface area of clay, almost at the same time, Lu and co-workers put forward some new ideas on the design of hydrogels for water purification inspired by the catechol−ferric ion complexes in marine mussel adhesive fibers.189 The adsorption capacity of the as-prepared hydrogel was investigated using a red dye Rh6G as a model. The hydrogel was filled in a plastic syringe, and Rh6G-containning water was slowly poured into the plastic syringe. A complete color fading of the water was observed, suggesting the removal of the dye from the water. The maximum adsorption capacity of the resultant hydrogel toward Rh6G was determined to be 150 mg/g. Besides Rh6G, this clay-based hydrogel can be used for isolation of a wide range of other contaminants from water. 7.2. Water/Oil Separation

With increasing environmental awareness and tighter regulations, there is an urgent need for novel strategies as well as new materials to separate oils from industrial wastewaters, polluted oceanic waters, especially oil-spill mixtures, which can quickly lead to serious and irrecoverable damage to the environment and the ecosystem.366 Oil absorption using 5100


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immobilized with amine-liposomes incorporated by AquaporinsZ, a member of the family of aquaporins, via the formation of an amine-catechol adduct. The water flux of the resultant membrane increased by 65%, and the rejection of NaCl and MgCl2 rose by 66.2% and 88.1%, respectively, as compared to the pristine membrane.

Membrane-based technologies are also attractive for oil/ water separation, because they are relatively energy-efficient and applicable across a wide range of industrial processes. Researchers have recently found that polydopamine modification allowed the membranes to prevent oil from permeating. As an example, Freeman and co-workers demonstrated the use of polydopamine-modified commercial polyamide reverse osmosis membranes for oil/water separation and investigated the polydopamine modification conditions on the permeation flux during oil/water filtration.371 They found that both unmodified and modified membranes showed over 99.9% of organic rejection. Nevertheless, all polydopamine-modified membranes exhibited much higher water flux than unmodified membranes. Furthermore, the water flux could be controlled by varying the deposition time and the concentration of dopamine. Hu and his collegues reported a novel procedure to synthesize a new type of water separation membrane made of layer-by-layer deposition of GO nanosheets, which were cross-linked by 1,3,5-benzenetricarbonyl trichloride on a polydopamine-coated polysulfone support.372 In another interesting study, Cai and co-workers immobilized thiols and Ag nanoparticles on the surface of bottles with polydopamine as the interlayer.373 Organic pollutants were found to be rapidly enriched via the hydrophobic interaction with thiols and/or π−π stacking interactions with the polydopamine layer. In this strategy, not only oil/water separation, but also long-term storage of water has been achieved, which is highly beneficial for online and in situ analysis.

8. SENSING APPLICATIONS 8.1. Polydopamine as the Grafting Material for Sensing Applications

Electrochemical biosensors have seen significant growth in the past few years due to their many advantages involving simple instrumentation and operation, high sensitivity and selectivity, and wide linear range.377 From the perspective of electrochemical reactivity, polydopamine has the ability to provide a suitable microenvironment for highly dense immobilization of biomolecules on surfaces such as electrodes while retaining their biological activities. The immobilization is essential for the operation of the biosensor, which is an important challenge in constructing biosensing systems, and plays a key role in the selectivity, sensitivity, as well as the stability of biosensors. Consequently, tremendous efforts have been dedicated to fabricating high-performance polydopamine-based electrochemical biosensors.378−412 In general, most polydopaminebased biosensors can be manufactured through three major approaches as follows: (i) direct encapsulation of biomolecules during polymerization of dopamine; (ii) post modification of biomolecules on polydopaminemodified electrodes based on versatile polydopamine chemistry; and (iii) the use of polydopamine as the building block for the fabrication of the electrode materials, which is directly used for biosensing applications. 8.1.1. Detection of Small Organic Molecules. Zheng et al. described a reproducible sensor using an electropolymerized polydopamine film on the surface of a bilayer lipid membrane, which was preimmobilized with horseradish peroxidase (HRP) for rapid and sensitive detection of H2O2 at the submicromolar level.378 The outer polydopamine film on the bilayer lipid membrane surface could retain the structure of the bilayer lipid membrane as well as protect the HRP enzyme from deactivating and prevent the leakage of HRP enzyme from the bilayer lipid membrane, leading to the greatly enhanced stability of the bilayer lipid membrane biosensor. When the proposed sensor was exposed to successively increasing concentrations of H2O2 within a specific range (2.5 × 10−7 to 3.1 × 10−3 M), the electrocatalytic reduction current increased in a linear fashion. Further, it was found that the coverage of polydopamine on the bilayer lipid membrane could hinder the interfering species from diffusing to the electrode surface, resulting in high selectivity. This principle was illustrated by testing the interferential effects of three compounds, ascorbic acid, L-cysteine, and glycine, which are the three main interfering substances during the detection of H2O2. Results showed that even a 40-fold excess of these three interfering compounds did not induce any effect on the measurement of H2O2. Thereafter, several other types of H2O2 electrochemical sensors have also been reported. Wang et al. utilized ZnO microspheres as sacrificial templates to produce monodisperse polydopamine−Ag hybrid hollow microspheres.379 The polydopamine−Ag hollow microspheres-modified electrode dis-

7.3. Seawater Desalination

The global shortage of fresh water, due to ever growing water consumption, global warming, and water contamination, is one of the greatest challenges that humanity encounters today. In addition to oil/water separation, membrane techniques have also attracted attention in the desalination of seawater to address the global freshwater crisis. The forward osmosis (FO) technique that is related to osmotic pressure difference is of great advantage as compared to conventional pressure-driven membrane processes such as nanofiltration and reverse osmosis, because this technique can reduce energy consumption and equipment cost and increase the water recovery.374 Nevertheless, the inadequate number of commercially available FO membranes with high performance as well as their low salt rejection significantly restricts the introduction of FO into the technology market. Recently, Chung and coworkers applied a thin coat of polydopamine on the surface of the commercially available FO membrane and found that the polydopamine-modified membranes showed a dramatic increase in the water permeability and salt rejection when compared to pristine membranes.375 Such an enhancement was ascribed to the polydopamine coating-induced increase of hydrophilicity of both the membrane surface and the pore-wall inside of the substrate layer, and interaction of polydopamine with the monomer, which is highly beneficial for the formation of membranes with a high salt rejection property. To address the high energy-consumption associated with conventional pressure-driven membrane processes, more recently, the same group focused their sights on the fabrication of membranes for nanofiltration, inspired by the biological membranes that comprise aquaporins with extraordinary water permeability and selectivity.376 The conventional membrane was first modified with polydopamine, and subsequently 5101


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applied in the fabrication of electrochemical sensors for simultaneous detection of hydroquinone and catechol.388 To further improve the sensitivity, an electrochemical, signal amplified immunosensor has been recently developed for the determination of 3-bromobiphenyl by using polydopaminecoated gold nanoclusters as the sensor platform and multienzyme-labeled hollow carbon nanochains as the signal amplifier. The detection limit reached as low as 0.5 pM.389 Besides the aforementioned functionalities, polydopamine has also been used as the carbon resource to prepare nitrogendoped carbon material-based electrochemical sensing systems. For instance, Chen and co-workers synthesized hollow nitrogen-doped carbon microspheres by pyrolysis of polydopamine-coated SiO2 microspheres, followed by HF etching.390 A competitive assay toward the oxidation of uric acid, ascorbic acid, and dopamine illustrated that the polydopamine-derived carbon microspheres had catalytic activity superior to that of other carbon materials such as CNTs. Moreover, the oxidation peak potentials of these three organic molecules were completely separated, enabling the simultaneous determination of these three compounds in the same system. The detection limits for uric acid, ascorbic acid, and dopamine were 0.04, 0.91, and 0.02 μM, respectively. In a following study, the authors decorated Au nanoparticles on the resultant hollow carbon microspheres and subsequently modified thiolated-β-cyclodextrin (HS-β-CD) to yield an electrochemical sensor for highly effective detection of naphthols.391 8.1.2. Detection of Biomolecules. Over the past few years, there have been many literature reports regarding the polydopamine-based electrochemical biosensors for the detection of biomolecules.392−397 An extremely important example is in the detection of saccharide. For example, Gao and coworkers have developed a glucose electrochemical biosensor using polydopamine-modified carbon nanotubes (CNTs).392 To accelerate the transfer of electrons between the electrode material and the underlying electrode, Ag nanoparticles were also decorated on the polydopamine-modified CNTs. The resultant Ag@polydopamine@CNT, together with glucose oxidase (GOx), was then cast on a cleaned glassy carbon electrode. Here, the polydopamine coating could not only remarkably improve the solubility of CNTs while not damaging their electronic structure, but also promote the electron transfer between the immobilized GOx and the underlying electrode. When the test system contains glucose, the enzyme-catalyzed reaction of glucose will cause a decrease of the oxygen reduction peak current, which can be employed to determine the glucose concentration. This biosensor showed a quite rapid response to glucose (

Polydopamine and Its Derivative Materials: Synthesis and Promising

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