Particles with Tunable Porosity and Morphology by Controlling

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Particles with Tunable Porosity and Morphology by Controlling Interfacial Instability in Block Copolymer Emulsions Kang Hee Ku, Jae Man Shin, Daniel Klinger, Se Gyu Jang, Ryan C. Hayward, Craig J. Hawker, and Bumjoon J. Kim ACS Nano, Just Accepted Manuscript • DOI: 10.1021/acsnano.6b00985 • Publication Date (Web): 03 May 2016 Downloaded from http://pubs.acs.org on May 8, 2016

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Particles with Tunable Porosity and Morphology by Controlling Interfacial Instability in Block Copolymer Emulsions Kang Hee Ku1, 2, Jae Man Shin1, Daniel Klinger2, 3, Se Gyu Jang4, Ryan C. Hayward5, Craig J. Hawker2,*, Bumjoon J. Kim1,*

1

Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science

and Technology (KAIST), Daejeon 305-701, Republic of Korea 2

Materials Research Laboratory, University of California, Santa Barbara, California 93106,

United States 3

Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Str. 2-4, Berlin 14195, Germany

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Soft Innovative Materials Research Center, Korea Institute of Science and Technology (KIST),

Jeonbuk, 565-905, Republic of Korea 5

Department of Polymer Science and Engineering, University of Massachusetts, Amherst,

Massachusetts 01003, United States

*E-mail: [email protected] (B.J.K.), [email protected] (C.J.H.)

ACS Paragon Plus Environment

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ABSTRACT A series of porous block copolymer (BCP) particles with controllable morphology and pore sizes was fabricated by tuning the interfacial behavior of BCP droplets in oil-in-water emulsions. A synergistic adsorption of polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) BCPs and sodium dodecyl sulfate (SDS) to the surface of the emulsion droplet induced a dramatic decrease in the interfacial tension and generated interfacial instability at the particle surface. In particular, the SDS concentration and the P4VP volume fraction of PS-b-P4VP were key parameters in determining the degree of interfacial instability, leading to different types of particles including micelles, capsules, closed-porosity particles, and open-porosity particles with tunable pore sizes ranging from 10 to 500 nm. The particles with open-porosity could be used as a pH-responsive, high capacity delivery systems where the uptake and release of multiple dyes could be achieved.

KEYWORDS porous particle, block copolymer, interfacial instability, emulsion droplet, drugdelivery


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Colloidal particles with porous morphologies have attracted significant attention due to their high surface-to-volume ratio, thus giving rise to potential applications such as drug-delivery systems,1-3 chromatography media,4-5 nano-reactors,6-7 and small-molecule carriers.8-12 Over the past decades, several approaches have been employed for the fabrication of porous polymeric particles such as suspension polymerization using high internal phase emulsions techniques,13-15 seeded dispersion polymerizations,16-19 and emulsion polymerization.20-21 In particular, selfassembled block copolymers (BCPs) were used as templates to create porous nanostructures either by selectively removing one of the blocks through etching processes including UV/ozone,22-25

or by the selective extraction of small molecules that were non-covalently

bonded to the BCPs.26-28 In addition, the surface reconstruction of poly(styrene-b-vinylpyridine) copolymers has been applied to produce porous structures by exposure to solvents that have different affinities for each block.29-32 Recently, an effective approach which takes advantage of the hydrodynamic instabilities at the interface of oil-in-water emulsions has been reported for producing colloidal porous particles.33-37 For an oil droplet containing amphiphilic BCPs, the strong adsorption of the amphiphilic BCPs at the oil/water interface induces dramatic decreases in interfacial tension, leading to a hydrodynamic ‘interfacial instability’. As a consequence, the spontaneous growth of the interfacial area drives significant undulation of the droplet surface, which can lead to ejection of smaller droplets and the fabrication of various micellar structures (i.e., spherical micelles, worm-like micelles, and vesicle structures).37-40 However, less attention has been paid to the development of porous BCP particles using this strategy, although systematic control of interfacial roughening can potentially generate BCP particles with more varied pore structures and sizes.36 As an added challenge in this study and to fully exploit the potential of porous


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particles with high surface area, structures with stimuli-responsive functional groups on the surface were targeted for uptake and release applications. Herein, we report a powerful strategy for the preparation of porous particles with tunable nanostructures and porosities using polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) BCPs. Key to the success of this strategy is the ability to systematically control the interfacial instability of the oil-in-water emulsion droplets by adjusting both the concentration of surfactant (sodium dodecyl sulfate (SDS)) and the architecture of BCPs (i.e. volume fraction of P4VP (fP4VP) and molecular weight). It was observed that the synergistic contribution from the adsorption of both PS-b-P4VP and SDS at the interface was crucial to driving the interfacial tension close to zero, thus generating the interfacial instability, which leads to BCP particles with desired porosity and pore size. Moreover, the utilization of the functional P4VP block allows these porous particles to be used as stimuli-responsive carriers for the pH-dependent loading and release of active small molecules.


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RESULTS AND DISCUSSION

Figure 1. (a) Dependence of particle morphology on cSDS values. Electron micrographs of the porous PS27k-b-P4VP7k particle (open-porosity particle obtained at 0.4 wt% of cSDS): (b) SEM; (c) TEM; (d) cross-sectional TEM; (e) TEM slices extracted from the full reconstructed 3D image from TEM tomography; and (f) reconstructed 3D image from TEM tomography. The samples for TEM measurements were stained by iodine vapor, where the dark region is P4VP domain.

To generate porous particles, it is of critical importance to reduce the interfacial tension between the BCP droplets and the surrounding water in the toluene-in-water emulsion. This can be achieved by controlling the concentration of SDS (cSDS) and the molecular architecture of the


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amphiphilic PS-b-P4VP polymers. To investigate these parameters separately, we first explored the morphology of PS27k-b-P4VP7k BCP particles by varying the SDS concentration (cSDS) from 0.05 to 1 wt%. For a fixed BCP architecture (the molecular weight (Mn) = 34 kg/mol, fP4VP = 0.2), a 1 wt% solution of the BCP in toluene was emulsified into aqueous solutions of SDS using a homogenizer. The sizes of the initial emulsion droplets were ranging from 1 to 20 µm with an average droplet size 10.1 ± 2.4 µm. Subsequent slow evaporation of toluene (stirred for 3 days at room temperature) led to droplet shrinkage until solidified polymer particles with the same internal structure but with various sizes (from 300 nm to 4 µm) are produced. To avoid the deformation of emulsions during the solvent evaporation process, the size of initial emulsions was controlled to be larger than 1 µm. Figure 1(a) shows transmission electron microscopy (TEM) images of the PS27k-b-P4VP7k particles for different cSDS values. At a low cSDS value of 0.05, spherical BCP particles with an internal nanostructure of P4VP spheres dispersed in a PS matrix were produced. However, no porosity was observed. Interestingly, an increase of cSDS to 0.1 wt% resulted in the formation of closed-porosity particles, spherical particles with nanometer-sized pores inside the particles. A further increase in the cSDS value to 0.2 wt% resulted in BCP particles with open-porosity with the connected structure being maintained even when cSDS was increased to 1.0 wt% - above the critical micelle concentration (CMC) value of SDS. In these cases, a connected porous morphology stretches from the particle surface to the core of the particles as shown by scanning electron microscopy (SEM) and TEM (Figures 1(b) and (c)). Additionally, cross-section TEM imaging (Figure 1(d)) shows that the particles contain PS walls of 20 nm thickness (light grey regions), which creates pores with average inner diameter of 89 ± 21 nm. The inside of these pores consist of collapsed P4VP chains (dark gray regions, stained with iodine vapor). The reconstructed 3D image acquired from TEM


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tomography (Figures 1(e), (f) and Figure S1) further highlights the open-porosity structure with continuous PS walls with P4VP chains at the surface of the porous structure (Tomography movie can be found in the Supporting Information). As a consequence, the responsive pyridine groups of the P4VP domains are accessible on the pore surfaces.

Figure 2. (a-d) Schematic illustration for the fabrication of porous particles through oil-in-water emulsion. Inset figures are the fluorescent optical microscopy images of the evolution of PS-bP4VP emulsion droplets with dye molecules (Nile red for toluene phase, and fluorescein for water phase) under irradiation at 365 nm.

These experiments show that porosity formation is highly dependent on the cSDS values and can be explained by the following mechanism. In this process, the generation of porous structures is driven by the interfacial instability of the toluene-in-water emulsion (see schematic illustration in Figure 2(a)-(d)). Initially, the amphiphilic SDS molecules adsorb at the interface between the polymer solution and water when the BCP solution in toluene is emulsified in the aqueous SDS solution (Figure 2(a)). As the toluene evaporates from the emulsion droplet, the concentration of PS-b-P4VP BCPs increases, and more amphiphilic PS-b-P4VP polymers adsorb at the emulsion droplet/water interface (Figure 2(b)). The synergistic adsorption of both PS-bP4VP and SDS molecules at this interface leads to a dramatic decrease in interfacial tension (γ) between the emulsion droplets and the water. Ultimately, the γ approaches zero (Figure 2(c)), and, at this stage, the free energy penalty for increasing the surface area of the emulsion droplets


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becomes negligible. This leads to the generation of spontaneous undulation at the surface of the droplets, similar to other processes involving interfacial roughening through the addition of surfactants. For immiscible fluids such as oil/water systems41 and polymer blends,42-44 a reduction of γ value between the two different phases close to zero triggers an increase in the interfacial area and allows the system to evolve toward its equilibrium microemulsion structure.45-46 In the presented PS-b-P4VP system, the interfacial roughening allows small water droplets to infiltrate the BCP-containing toluene droplet by forming water-in-oil-in-water double emulsions stabilized by both SDS and PS-b-P4VP (Figure 2(d)). This hypothesis can be supported by fluorescent optical microscopic images of the BCP emulsion droplets. To enhance contrast between toluene and water phases in the emulsion, we added Nile red and fluorescein dyes into toluene and water phases, respectively. Inset figures in Figure 2 visualized that multiple small green-colored water droplets were formed inside the red-colored toluene emulsions as toluene evaporated. Finally, after all of the toluene was evaporated, these small water droplets resulted in the observed porous structure with pore sizes much larger than the periodicity of the BCPs.


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Figure 3. Interfacial tension (γ) values for oil/water interfaces with i) pure toluene (●) and ii) 1 wt% toluene solutions with different PS-b-P4VP polymers (PS27k-b-P4VP7k (■), PS15k-b-P4VP7k (▲), and PS9.8k-b-P4VP10k (◆)). The γ value was measured by pendant drop method.

As stated above, this mechanism is based on a very low interfacial tension between the toluene and the water phase and, for a given BCP concentration and architecture, this parameter crucially depends on the cSDS values. To investigate this influence quantitatively, the γ values at the toluene/water interface were determined via pendant drop tensiometry for a series of four different toluene solutions with 1 wt% PS27k-b-P4VP7k (fP4VP = 0.20), 1 wt% PS15k-b-P4VP7k (fP4VP = 0.32), and 1 wt% PS9.8k-b-P4VP10k (fP4VP = 0.50). These results are compared to pure toluene for a range of SDS concentrations - cSDS was varied from 0.01 to 0.4 wt%. As expected (see Figure 3), γ was greatly influenced by cSDS with γ decreasing significantly due to the enhanced adsorption of the surfactant at the toluene/water interface. The γ values reached


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constant values near the CMC of SDS (0.23 wt%) with additional surfactant accumulating predominantly in the micelles and not at the toluene/water interface. In addition, compared to the γ values for pure toluene, the presence of PS27k-b-P4VP7k led to a greater reduction of the interfacial tension. However, this difference between the γ values with and without PS27k-bP4VP7k BCP decreased at higher cSDS, suggesting that as more SDS was adsorbed at the interface, a fraction of the PS-b-P4VP was displaced. While it is assumed that the generation of porous particles synergistically depends on the adsorption of both PS-b-P4VP and SDS molecules at the droplet surface, it becomes obvious that for a constant concentration of the PS27k-b-P4VP7k, the cSDS determines the morphology (see Figure 1). At cSDS = 0.05 wt%, γ was 16.2 mN m-1 and evolution of the toluene droplets did not show instabilities of the toluene/water interface, thus leading to spherical particles without any porous structures. An increase of cSDS to 0.1 wt% lowered the value of γ to 7.8 mN m-1, and a few nanometer-sized pores began to form inside the spherical particles. The presence of this closed-porosity structure suggests that slight interfacial roughening occurred during solvent evaporation. Further increasing cSDS to 0.2 wt% lowered the value of γ to 4.2 mN m-1, and open-porosity structures were obtained. This result indicates a much greater effect due to a denser adsorption of SDS molecules at the toluene/water interface. Note that, for the pendant drop tensiometry experiments, the γ value was measured at a fixed value of BCP concentration (1 wt%). As the toluene was evaporated during the formation of the BCP particles, the BCP concentration in the toluene increased significantly and the γ values shown in Figure 3 were therefore overestimated compared to those of the emulsions in the actual experiment. Thus, in-situ measurement of the γ value during the evaporation of the toluene, which increases the BCP concentration, would be required to estimate the actual γ value of the BCP droplets and to determine the onset point of interfacial instability in terms of cSDS.35


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For all PS-b-P4VP polymers, the trend of decreasing γ values as the cSDS increased was observed with PS-b-P4VP polymers having larger fP4VP values leading to a greater reduction of the γ values. The measured values of γ in the absence of SDS were 34.9 mN m-1 without PS-bP4VP (literature value: 35.2 mN m-1),47 31.1 mN m-1 with 1 wt% PS27k-b-P4VP7k (fP4VP = 0.20), 27.2 mN m-1 with 1 wt% PS15k-b-P4VP7k (fP4VP = 0.32), and 23.9 mN m-1 with 1 wt% PS9.8k-bP4VP10k (fP4VP = 0.50) (Supporting Information Table S1). In particular, the symmetric PS9.8k-bP4VP10k diblock copolymer produced lower γ values for the entire range of SDS concentrations than the PS-b-P4VP BCPs with lower fP4VP values (PS15k-b-P4VP7k and PS27k-b-P4VP7k). This relationship between polymer structure, the reduction of γ value and the final morphology of the particle, which will be discussed in detail below.


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Figure 4. SEM (a-d) and TEM (e-h) images of different PS-b-P4VP particles: (a, e) PS116k-bP4VP4k (fP4VP = 0.03), (b, f) PS40k-b-P4VP5.6k (fP4VP = 0.12), (c, g) PS15k-b-P4VP7k (fP4VP = 0.32), and (d, h) PS9.8k-b-P4VP10k (fP4VP = 0.50). Different types of particles were obtained in terms of fP4VP values: (a) closed-porosity particles, (b) open-porosity particles, (c) capsules, and (d) connected micelles. The scale bars are 300 nm.

Table 1. Characteristics of PS-b-P4VP BCPs Used in This Study. PS-b-P4VP BCPs PS116k-b-P4VP4k PS40k-b-P4VP5.6k PS27k-b-P4VP7k PS50k-b-P4VP13k PS109k-b-P4VP27k PS190k-b-P4VP45k PS50k-b-P4VP17k PS15k-b-P4VP7k PS9.8k-b-P4VP10k

Mn [kg/mol] 120 45.6 34 63 136 235 67 22 19.8

PDI 1.07 1.10 1.15 1.08 1.12 1.18 1.15 1.18 1.08

fP4VP 0.03 0.12 0.20 0.20 0.20 0.20 0.25 0.32 0.50

The particle morphology was found to crucially depend on the synergistic co-adsorption of both SDS and PS-b-P4VP at the droplet interface. Having demonstrated that for a given PS-bP4VP architecture the particle porosity increases with increasing cSDS, the influence of the PS-bP4VP architecture on the γ value and the morphology of BCP particles was studied. A series of BCP particles was therefore produced using five different PS-b-P4VP copolymers with different fP4VP: PS116k-b-P4VP4k (fP4VP = 0.03), PS40k-b-P4VP5.6k (fP4VP = 0.12), PS27k-b-P4VP7k (fP4VP = 0.20), PS15k-b-P4VP7k (fP4VP = 0.32), and PS9.8k-b-P4VP10k (fP4VP = 0.50) (The characteristics of the PS-b-P4VP BCPs used in this study are summarized in Table 1). To ensure the low γ value required for the generation of porous structures, the optimized processing conditions for the porous PS27k-b-P4VP7k particles were used (cSDS of 0.4 wt%). Figure 4 shows the SEM and TEM images of the particles produced by emulsifying solutions of five different BCPs. For the lowest P4VP content (fP4VP = 0.03) spherical particles with non-porous surfaces were obtained. However, pores were observed inside the particles (closed-porosity particles, Figures 4(a) and


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(e)) and the average diameter (d) of the inside pores was measured to be 10 nm. When the fP4VP value was increased to 0.12 (PS40k-b-P4VP5.6k), open-porosity particles were produced with pores both at the surface and in the interior of the particles (Figures 4(b) and (f)). This morphology is identical to the open-porosity structures previously obtained for the PS27k-bP4VP7k particles (fP4VP = 0.2). However, interestingly, the d values of the open-porosity particles dramatically increased from 10, 35, and 89 nm with increasing fP4VP for PS116k-b-P4VP4k, PS40kb-P4VP5.6k, and PS27k-b-P4VP7k, respectively. When fP4VP was increased further to 0.32 (PS15k-bP4VP7k), an interesting morphological transition was observed. Instead of spherical BCP particles, capsular and spherical micellar structures were obtained (capsules, Figures 4(c) and (g)). These morphologies were very similar to the vesicles or micelles driven by hydrodynamic interfacial instability, which were observed earlier by Zhu et al..34, 36 For symmetric PS9.8k-bP4VP10k (fP4VP = 0.50), no particles were produced by emulsions, and, instead, connected micelles were formed (micelles, Figures 4(d) and (h)). These morphological transitions depending on fP4VP can be understood by considering the polymer’s preferred curvature at the toluene/water interface during interfacial roughening. As shown in the schematic illustration in Figure 4, the geometric shape of assembled PS-b-P4VP at the toluene/water interface determines the curvature of interfacial undulation at the BCP particle surface.33,

37, 48-49

At a small fP4VP, reduction of γ generates surface undulations with a large

curvature, allowing only a minor amount of water infiltration into the P4VP core of the PS-bP4VP micelles, resulting in the small-sized pores after water evaporation. As the fP4VP increases from 0.03 to 0.12, the periodicity of interfacial roughness increases to accommodate the larger P4VP fraction, thus generating a much larger undulation at the interface and allowing a larger degree of water infiltration into the P4VP cores. Further increasing the fP4VP to 0.32 generates a


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lower γ and a much stronger driving force for interfacial instability. In this case, the volume of water-infiltrated P4VP domain is expected to be larger than that of PS domain, inducing the ejection of the PS-b-P4VP micelles from the interface into the water phase.34,47 As a result, hundreds-nanometer-sized capsules were produced as shown in Figures 4 (c) and (g).36, 49-51 This evolution of the emulsion droplets also occurs at higher fP4VP (0.5), but the symmetric BCP structure leads to the formation of connected micelles. From these results it can be concluded that the degree of interface undulation and the ultimate structure of the water-swelled BCP assembly are both strongly dependent on fP4VP values which in turn are crucial in determining the structure of the BCP particles.


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Figure 5. Morphological transition of PS-b-P4VP particles plotted by cSDS vs. fP4VP. Different structures are denoted by different shapes and colors: red ◎ (micelles); yellow ● (capsules); green ▲ (open-porosity particles); blue ◆ (closed-porosity particles); and black ■ (spherical, nonporous particles).

As discussed in the previous section, both cSDS and fP4VP have a significant influence on controlling the interfacial instability and thus determining the morphology of PS-b-P4VP particles. To further expand the parameter space, we examined the morphology transition for particles from six different PS-b-P4VP BCPs with different fP4VP numbers as a function of cSDS values (see Figure 5 - TEM images for each point are shown in Figure S2). The resulting phase diagram illustrates a number of trends - for the lowest cSDS value (0.05 wt%), all particles showed


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a non-porous structure regardless of fP4VP. Spherical particles were also obtained as the amount of SDS was not sufficient to generate the required hydrodynamic interfacial instability. Interestingly, the inner structures of the spherical particles were different depending on fP4VP. At low values (fP4VP < 0.25) spherical P4VP micelles were formed inside of microparticles, while worm-like micelles were formed at fP4VP = 0.32. In contrast, for a higher cSDS regime, a clear difference in the particle morphology for different fP4VP was observed. At the lowest fP4VP (0.03), 0.1 wt% of cSDS did not induce any morphological transition and closed-porosity particles were observed even though cSDS was above the CMC value. In contrast, for higher fP4VP > 0.12, the cSDS value of 0.1 wt% does generate significant interfacial instabilities and induces a morphological transition to open-porosity. In particular, when fP4VP values were high (0.32 and 0.5), the capsules and the micellar structures were produced at the same cSDS = 0.1 wt%. Thus, the effect of cSDS on tuning the overall particle morphology was more dramatic for BCPs with higher fP4VP. At higher cSDS, each structure was maintained (e.g., closed-porosity particles at fP4VP = 0.03, open-porosity particles at fP4VP = 0.2, and vesicles at fP4VP = 0.32) showing no variation dependent on cSDS in a range from 0.2 to 1.0 wt%.


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Figure 6. SEM (a-d) and TEM (e-h) images of porous PS-b-P4VP particles: (a, e) PS27k-bP4VP7k; (b, f) PS50k-b-P4VP13k; (c, g) PS109k-b-P4VP27k; (d, h) PS190k-b-P4VP45k. All of the PS-bP4VP polymers have the same fP4VP value of 0.20. However, the sizes of the pores were measured to be 89 ± 21 nm, 172 ± 31 nm, 280 ± 45 nm, and 513 ± 97 nm, respectively. The scale bars are 1 µm.

The phase diagram in Figure 5 clearly demonstrates the existence of a window of fP4VP (between 0.1 and 0.2) for which open-porosity particles can be obtained when cSDS exceeds 0.1 wt%. While these conditions were shown to be reproducible, they only allow limited control over the pore size. As these features determine the utility of these materials for specific applications, strategies for tuning the pore size while maintaining the overall morphology of the particles (i.e., open-porosity) were investigated. A series of BCP particles was therefore prepared using four different PS-b-P4VP BCPs with different Mn values but with a constant fP4VP value of 0.2: PS27kb-P4VP7k, PS50k-b-P4VP13k, PS109k-b-P4VP27k, and PS190k-b-P4VP45k. As expected, these PS-bP4VP BCPs produced similar morphologies with SEM and TEM images in Figure 6 showing that the desired open porosity formed for all PS-b-P4VP BCPs. However, the size (d) of the pores clearly increased with increases BCP Mn, showing d = 89 ± 21, 172 ± 31, 280 ± 45, and


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513 ± 97 nm for PS27k-b-P4VP7k, PS50k-b-P4VP13k, PS109k-b-P4VP27k, and PS190k-b-P4VP45k, respectively. The investigated four different BCPs had same value of fP4VP, and thus almost same geometrical shape of undulation at the interface can be generated. However, the periodicity of fluctuation at the interface will be dependent on the radius of P4VP core and thus the Mn of the BCPs, which determines the d of pores in the BCP particles. It is remarkable that the difference of pore size between PS27k-b-P4VP7k and PS190k-b-P4VP45k is larger than 400 nm, clearly demonstrating the efficiency and power of this strategy for porous particles with tunable pore sizes.

Figure 7. Development of light-emitting, carrier particles from open-porosity particles of PS27kb-P4VP7k: (a) post-assembly loading of water-soluble dye molecules (fluorescein and rhodamine


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B); (b) in-situ loading of organic-soluble dye molecules (pyrene) during particle formation; (c-e) dynamic cargo exchange process by tuning pH values

The extremely large surface area of these porous particles can be used to load various small molecule biological and chemical-reagents, making them useful for drug delivery, nanoreactors, and as molecular carriers.52-54 An added benefit of the system design is that the P4VP chains allow for stimuli-responsiveness to be introduced.55-60 To demonstrate the potential of the porous particles as efficient carriers, we attempted to load the colloidal particles with various dye molecules. The use of small molecule dyes allows easy monitoring of the selective binding and release of multiple dyes from the porous particles. The initial mechanism studied was electrostatic interactions between carboxylic acid functionalized dyes (fluorescein and rhodamine B) and the basic 4VP groups.61 The porous particles were therefore dispersed in an aqueous solution containing either fluorescein (green emission, peak of wavelength (λ) = 512 nm) or rhodamine B (yellow emission, λ = 580 nm) and stirred overnight. Excess dye molecules, which did not bind with the particles, were then removed by repeated centrifugation and washing. As shown in Figure 7(a), green or yellow emitting particles were obtained, indicating the successful adsorption of dye molecules with the P4VP chains of the porous particles. To demonstrate the importance of the porosity in loading the cargo molecules, we compared the loading efficiency of the dyes in the porous particles with that of non-porous particles. Because the porosity of the particle would strongly depend on their size, same sized, monodisperse porous and non-porous particles were prepared by the membrane emulsification method.62 Interestingly, PS27k-b-P4VP7k porous particles had almost 10 times higher loading efficiency of the dye molecules than non-porous spherical P4VP particles. (See Figure S3 for details.)


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The porous structure of the particles could also be further utilized by exploiting the welldefined spatial arrangement of polymer domains with distinctly different properties: the responsive hydrophilic P4VP chains on the pore surface and the glassy inert PS walls. This allows for the selective functionalization/loading of each nanoscopic domain with different cargo molecules. Having demonstrated the ability of the pore surface to retain charged water soluble payloads, the hydrophobic PS domains offer the possibility to adsorb and retain water insoluble compounds. This functionalization can be achieved in situ by adding organo-soluble dye molecules to the BCP solution in toluene before emulsification with the organo-soluble dye molecules segregating to the hydrophobic PS domains on removal of the toluene. As a demonstration, blue light-emitting porous particles were fabricated from emulsion droplets that contained a mixture of PS-b-P4VP and pyrene solution (Figure 7(b)). Significantly, the porous particles containing pyrene could then be loaded with green-emitting fluorescein through ionic interactions with the P4VP functionalized pores. The successful incorporation of both cargoes was evident from the color of the BCP particles which showed a blue-green emission due to the pyrene inside the glassy PS walls and the fluorescein within the hydrophilic P4VP surface of the pores (Figure 7(c)). Furthermore, the electrostatic interactions between the water soluble dyes and the P4VP pore surfaces can be used to produce carrier particles with stimuli-responsive release and uptake. For example, by increasing the pH value to 12, both the P4VP chains and the fluorescein molecules were fully deprotonated and the resulting ionic interactions result in the pH-triggered release of fluorescein from the P4VP domains. As a result, the emission of the porous particles changes back to the blue color characteristic of pyrene (Figure 7(d)). This dynamic release method was fully reversible; change of the pH from 12 to 5 results in the re-loading of the dye


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molecules. After the complete release of fluorescein, yellow-emitting rhodamine B dyes can be incorporated into the pores of the pyrene-loaded particles demonstrating exchange of cargo molecules, leading to white-emitting particles containing both pyrene and rhodamine B (Figure 7(e)). During this process, the structure of the porous particles was maintained without any change, showing high stability and reusability as a broad particle-based carrier platform (Figure S3).


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CONCLUSIONS We describe a simple method for the formation of BCP particles with controlled porous morphologies. A series of PS-b-P4VP particles including closed-porosity, open-porosity particles, capsules and connected micelles was generated depending on the cSDS and fP4VP of PS-b-P4VP. Both factors affected the γ value at the emulsion droplet/water interface and allowed effective tuning of the hydrodynamic instabilities at the interface. In particular, a balanced adsorption of PS-b-P4VP and SDS at the interface of the emulsion particle was key to generating particles with a desirable open-porosity structure. Furthermore, we demonstrated the use of these porous particles as pH-responsive carriers for multiple, different families of small molecules with the efficient loading and release of anionic dyes. This scalable and facile route to creating a series of porous particles with tunable pore sizes, structures and functionalities will be highly beneficial in developing functional colloid-based materials.


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EXPERIMENTAL SECTION Materials. Polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) copolymers were purchased from Polymer Sources Inc. (polymer information is summarized in Table 1). Sodium dodecyl sulfate (SDS, Sigma Aldrich) and toluene (Sigma Aldrich) were used as received. Pyrene, fluorescein and rhodamine B (Aldrich, Fluka, Sigma Aldrich) were loaded into the porous particles. Inc. Deionized water (DI) was used in all experiments. Fabrication of porous PS-b-P4VP particles. The PS-b-P4VP copolymers were dissolved in toluene to produce a 1 wt% polymer solution. The polymer solution (0.15 mL) was emulsified in deionized water (DI water, 2 mL) containing 0.4 wt% of SDS using a homogenizer for 1 min at 20,000 rpm. The organic solvent was slowly evaporated at room temperature for 3 days. Then, the sample was washed with DI water to remove the large excess of remaining surfactants by repeated centrifugations at 12,000 rpm for 10 min, and redispersed in DI water for further characterizations. The pH values of emulsions were maintained above 6.0 during emulsification, solvent evaporation, and washing step. For preparation of BCP particles with different cSDS values, identical amount of aqueous solution (2 mL) was used to emulsify polymer solution (0.15 mL) under same condition of homogenizer (20,000 rpm). Fabrication of light-emitting porous particles. A) Post-assembly loading of water-soluble dye molecules. To load dye molecules into the P4VP domains of porous particles, porous particles (2mg) were dispersed into the aqueous solutions (DI water, 1 mL) including rhodamine B (1 mg) and fluorescein (1 mg), respectively. The samples were stirred overnight, and washed thoroughly with DI water to remove excess dye molecules by repeated centrifugations (10000 rpm, 10min). B) Loading organic-soluble dye molecules during assembly. Both pyrene (1mg) and PS27k-bP4VP7k (2 mg) were mixed for 24 hr in toluene (1 wt%). Then, pyrene-added polymer solution


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was emulsified with an SDS aqueous solution (0.4 wt% in DI water). After the solvent evaporation process, the particles were washed with DI water to remove excess dye molecules and surfactants. C) Dynamic cargo exchange by tuning pH values. Pyrene-loaded porous particles were dispersed in water containing fluorescein (2 mg), and stirred overnight. After washing the samples with DI water, the particles in Figure 7(c) were obtained. Then, 0.1 M NaOH solution was added dropwise to the particles to increase the pH values up to 12, and stirred for 6 hr. After washing the samples with DI water, the particles in Figure 7(d) were obtained. Finally, the particles were re-collected by centrifugation, and were re-used to load rhodamine B in water. After stirring overnight, the particles in Figure 7(e) were obtained after removing excess dye molecules by repeated centrifugations. Characterization. SEM images were taken with both FEI XL 30 and Hitachi S-4800. TEM was performed on both Tecnai FEI T20 and JEOL 2000 FX. The samples were prepared by dropcasting BCP particle suspensions onto silicon wafers and TEM grids coated with a 20-nm thick carbon film, respectively. The prepared samples were exposed to iodine vapor to selectively stain the P4VP domains of the PS-b-P4VP particles. To investigate the internal structures of the particles by cross-sectional TEM, the samples were prepared by drop-casting particle suspensions onto an epoxy film and allowing the solvent to dry. Then, the epoxy-supported films were cured in an oven at 60 °C for 24 h. The epoxy-supported films were then microtomed with a diamond knife at room temperature into 50 nm slices. Transmission electron tomography was performed on a FEI Tecnai Sphera operated at 200 kV by recording a tilt series of bright field images in the angle range from -70° to +70° with angle increments. For the reconstruction of the three-dimensional particle morphology, a simultaneous iterative reconstruction technique (SIRT) algorithm was used. Interfacial tension measurements were performed by Theta Lite with a


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profile of pendant drop and OneAttension control software for analysis of drop shapes. Fluorescent optical microscopy (Nikon, Eclipse 80i) was used to visualize the interfacial instability of emulsion droplets. PL spectra were obtained from a Horiba Jobin Yvon NanoLog spectrophotometer. The excitation wavelength was set at 365 nm, and a 10 mm quartz cuvette was used for the PL spectra.

ASSOCIATED CONTENT Supporting Information. Additional supporting TEM images, measured values of interfacial tensions, movie of tomography TEM and full 3D reconstructed image for the porous particles. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Authors *E-mail: [email protected] (B.J.K) *E-mail: [email protected] (C.J.H.)

ACKNOWLEDGEMENT We gratefully acknowledge Stephan Kraemer at U. C. Santa Barbara for the tomography TEM and Prof. Otger Campas at U.C. Santa Barbara for the measurements of interfacial tension. This research was supported by the National Research Foundation Grant (2013R1A2A1A03069803), funded by the Korean Government and by the Institute for Collaborative Biotechnologies through grant W911NF-09-0001 from the U.S. Army Research Office (DK and CJH). The


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Particles with Tunable Porosity and Morphology by Controlling

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