Compartmentalized Hollow Silica Nanospheres Templated from

Jan 9, 2013 - We will show in this paper that silica templating of a nanoemulsion system results in compartmen- talized hollow silica nanospheres (HSN...
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Compartmentalized Hollow Silica Nanospheres Templated from Nanoemulsions Si-Han Wu,† Yann Hung,† and Chung-Yuan Mou*,†,‡ †

Department of Chemistry and ‡Center for Condensed Matter Sciences, National Taiwan University, Taipei, Taiwan 10617 S Supporting Information *

ABSTRACT: Nanoemulsions with very high stability can be created by ultrasonication using a rich variety of surfactants, oils, and solution conditions. Multicompartments within a nanoemulsion droplet can also be created via a carefully chosen surfactant system. We will show in this paper that silica templating of a nanoemulsion system results in compartmentalized hollow silica nanospheres (HSN) of sub-100 nm size under neutral pH conditions. The system consists of water, cetyltrimethylammonium bromide (CTAB), tetraethyl orthosilicate, n-hexadecane, n-octane, and n-hexanol. Two types of HSN can be obtained by manipulating the formulation; one is named single-compartment HSN (SC-HSN), where the HSN encapsulate a single water-in-oil droplet; the other is multiplecompartment HSN (MC-HSN), where the HSN encapsulate multiple smaller HSN. Using a high concentration of CTAB, we obtained a transparent solution of narrow size-distributed ultrasmall HSN (US-HSN) with a diameter of 12 nm. Parameters involved in the nanoemulsion have been examined and a possible mechanism is proposed. We show further that various new types of nested interior structures within HSN could be created by using other block copolymer type surfactants. Changing the oils to various food oils can also lead to biocompatible multicompartmentalized hollow silica nanospheres. A potential application of SC-HSN as a codelivery system of hydrophilic and hydrophobic drugs was demonstrated in simulated body fluid (SBF) using oil-soluble and water-soluble dyes as model compounds. Finally, we consider the mechanism responsible for the rich varieties of the nested structure in HSN and discuss factors promoting the stability of the nanoemulsion system for easy templating with ultrason-induced sol−gel silica chemistry. KEYWORDS: nanoemulsion, double emulsion, silica, hollow, nanosphere, drug delivery

1. INTRODUCTION Creating hollow nanospheres with nested interior space will be highly fascinating; such a ‘‘box-within-a-box’’ will be useful as a complex nanoreactor or a drug delivery agent. It will be even more useful if one can make the nested structure “permanent” with porous silica, using the soft multiple emulsions as templates. A large number of reports have demonstrated the fabrication of nanostructured silica templated by surfactant selforganization through sol−gel processes. The surfactant selforganization could be isolated micelles,1 vesicles,2 microemulsions3 and various lyotropic liquid crystalline phases.4 The templating of lyotropic liquid crystal has led to the development of many types of mesoporous silica materials.5 All of these approaches create void space surrounded by silica walls. The structures of the particles may include periodically arranged mesopores or isolated hollow spheres. Nanosized hollow silica spheres have been receiving a lot of attention6 recently because of their possible applications in nanomedicine,7 catalysis,8 and transparent coating.9 Synthesis of these spheres often involves silica condensation around some templates, such as solid spheres10 or emulsion droplets.11 However, the size of the hollow sphere as determined by the size of the template is often in the micrometer size regime. For © 2013 American Chemical Society

biomedical applications, one would prefer a size around 100 nm or less for the nanomaterials to be well-suspended in solution and capable of encapsulating cargo, such as catalytic nanoparticles8a,b,12 or enzyme molecules.13 Going one step further, an intriguing idea would be to create hollow silica nanospheres to encapsulate immiscible liquids within a combination of water and oil such that a water-in-oilin-silica-in-water (W/O/Silica/W) configuration could be achieved. Alternatively, one could simply encapsulate smaller hollow silica nanospheres within larger hollow spheres. This is like a W/O/W double emulsion system except that the two interfaces are coated with porous silica shell, e.g., W/Silica/O/ Silica/W. This kind of system would be highly desirable for drug delivery applications because it could simultaneously carry water-soluble and oil-soluble drugs. There have been many reports on double emulsion systems,14 either of the O/W/O type or the W/O/W type.15 In the few reported W/O/W systems, however, either the sizes are too big for biomedical applications (micrometer size)15a−c or the surfactants employed Received: September 26, 2012 Revised: January 6, 2013 Published: January 9, 2013 352

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are anionic15d and, thus, do not bind well with anionic silicates in sol−gel processes. In recent years, a lot of efforts have been devoted to designing multicompartment architectures, including micelles,16 liposomes-in-liposomes (vesosomes),2b,17 polymersomes-inpolymersomes,18 capsosomes19 and multilayer polymer capsules.20 In particular, using a capillary microfluidic coinjection approach, Weitz and co-workers could precisely control multiple emulsions with desired numbers and sizes of encased droplets.21 In addition, through dewetting of the middle phase of double-emulsions, polymersomes can be fabricated. Subsequently, polymersomes-in-polymersomes, which enable encapsulation and sequential release of multiple distinct components within spatially defined environments, were fabricated.18b Vogel and co-workers developed a vesosome structure, where small unilamellar vesicles (SUV) with different lipid-phase transition temperatures (Tt) were incorporated into a large unilamellar vesicle (LUV). With this structure, they successfully demonstrated that SUV encapsulated substrates can be released at each SUV’s particular Tt, allowing for controlled, consecutive enzymatic reactions within the same nanoreactor.17 Caruso and co-workers designed a new class of multicompartment capsules, named as capsosomes, based on layer-by-layer assembly of liposomes and polymers onto particle templates.19a This system was then further optimized for in situ enzymatic catalysis upon temperature triggering.19b,22 Although the above-mentioned multicompartment carriers have been developed elegantly and utilized nicely in vitro, it is noted that these materials are too large in size (from a few micrometers to hundreds of micrometers in diameter) to be useful for future in vivo applications. Our approach is to template nanoemulsion created by means of strong ultrasonic agitation. Among the various emulsions, nanoemulsions differ from common macroemulsions (droplet size >1 μm) in that they form almost transparent systems in which droplet sizes range from 30 to 200 nm.23 On the other hand, nanoemulsion is different from microemulsion as a nonequilibrium system, requiring energy input in its production. Often, nanoemulsions can be suspended better than microemulsions in the presence of destabilization agents (such as salts) after strong energy flow (such as ultrasound) is delivered.24 In recent years, nanoemulsion has attracted increased attention, yielding improvements in formulation, characterization and underline basic principles.25 Among the new developments in nanoemulsion, double nanoemulsion is particularly interesting. Its physical chemical properties and formation mechanism are not quite understood. But it is opening up many applications in several fields such as pharmaceuticals, foods, and cosmetics.25 However, only few studies have been reported using nanoemulsion as a template in making silica nanostructures.26 In this work, we created a W/ O/W nanoemulsion by ultrasonicating an oil−water−surfactant system in the presence of tetraethyl orthosilicate (TEOS). We describe a simple nanoemulsion system made from the common cationic surfactant cetyltrimethylammonium bromide (CTAB) and several oils.26a The oils are selected n-alkanes or some biocompatible vegetable oils and the silica source is tetraethyl orthosilicate (TEOS). First, we use an emulsion system, consisting of water (H2O), cetyltrimethylammonium bromide (CTAB), tetraethyl orthosilicate (TEOS), n-hexadecane (C16), n-octane (C8), and n-hexanol (C6OH), to produce the compartmentalized hollow silica nanospheres (HSN) with ultrasonication. Two types of HSN can be obtained by

manipulating the formulation; one is called single-compartment HSN (SC-HSN), where HSN encapsulate a single W/O droplet, obtained through an intermediate state of W/O/W double emulsions with a single inner W/O droplet (sW/O/W); the other is multiple-compartment HSN (MC-HSN), where HSN encapsulate multiple HSN, acquired through the intermediate state of W/O/W double emulsions with multiple inner W/O droplets (mW/O/W). Scheme 1 gives an outline of Scheme 1. Flow Chart of the Synthesis of Compartmentalized Hollow Silica Nanospheres (HSN)

a one-step synthesis involved in the synthesis of the compartmentalized hollow silica nanospheres. Detailed experimental procedures will be given in the Experimental Section. For the purpose of applications in drug delivery, we further studied two aspects of our multicompartmentalized HSN: using biocompatible oils in making HSN and simultaneous delivery of hydrophilic and hydrophobic model drug compounds. We show that many edible food oils, when replacing alkanes, can also be used in making the compartmentalized HSN. With the MC-HSN synthesized in this work, we can simultaneously encapsulate hydrophobic and hydrophilic compounds and found they can be released simultaneously in a dissolution process.

2. EXPERIMENTAL SECTION 2.1. Chemicals and Reagents. All reagents were used as received without further purification. Cetyltrimethylammonium bromide (CTAB, 99+%), tetraethyl orthosilicate (TEOS, 98%), n-hexadecane (C16, 99%), n-octane (C8, 99+%), n-hexanol (C6OH, 98%), rhodamine B, pyrene, Brij98, Triton X-100, olive oil, coconut oil and corn oil were purchased from Acrös. IGEPAL CO-520, peanut oil, sunflower seed oil and soybean oil were purchased from Sigma-Aldrich. Ultrapure deionized (D.I.) water was generated using a Millipore Milli-Q plus system. Quantum dot (Qdot 605 ITK amino (PEG) quantum dot, 8 μM solution) was purchased from Invitrogen. Simulated body fluid (SBF) was prepared according to a reported protocol developed by Kokubo et al.27 2.2. Synthesis of Single-Compartment Hollow Silica Nanospheres (SC-HSN). To obtain SC-HSN, a formulation consisting of a 227000/1/132/6.9 molar ratio for H2O/CTAB/TEOS/C16 was used. Typically, 9 mg of CTAB dissolved in 100 mL of D.I. water was prepared in a 250-mL bottle (Schott Duran) at room temperature. Then, an oil-phase solution containing 730 μL of TEOS and 50 μL of n-hexadecane was added to the aforementioned aqueous solution with stirring at 1000 rpm for 5 min to generate a simple oil-in-water (O/W) emulsion system. The reaction mixture was then sonicated using an ultrasonic bath (Branson 2510R-DTH Ultrasonic Cleaner, 100 W, 42 kHz), accompanyed with mechanical stirring at 1000 rpm (IKA, EuroST D S1) for 15 min at room temperature. After that, a cloudy mixture was obtained and then left to stand for another 24 h. The SC-HSN were isolated by centrifugation at 15 000 rpm for 30 min. The product obtained was further washed in sequence with ethanol and D.I. water to remove unreacted chemicals. In a similar manner, compartmentalized could be obtained by substituting n-alkanes with 400 μL of various vegetable oils, such as soybean, sunflower, peanut, olive, coconut, and corn oil. 2.3. Synthesis of Hydrophobic Magnetite Nanocrystals (Fe3O4). Hydrophobic Fe3O4 nanoparticles (10 nm) were synthesized using a seed growth method with a high-temperature solution-phase 353

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Figure 1. (a) TEM image of SC-HSN (enlarged in inset); (b) hydrodynamic diameter distribution of SC-HSN (polydispersity index = 0.12); (c) TEM image of SC-HSN after calcination (designed as SC-HSN_C); (d) N2 adsorption and desorption isotherms of SC-HSN and SC-HSN_C. reaction of Fe(acac)3 in benzyl ether in the presence of 1,2dodecanediol, oleic acid, and oleylamine as developed by Sun et al.28 Finally, a dispersion of oleic acid and oleylamine-capped Fe3O4 nanocrystals in octane was prepared for the following experiments. 2.4. Synthesis of Large SC-HSN Labeled with Hydrophilic Quantum Dot and Hydrophobic Pyrene (QD/Py@SC-HSN). To obtain large SC-HSN, a formulation consistng of H2O/CTAB/TEOS/ C16/C8 with a 227000/1/132/6.9/87.8 molar ratio was used, and low mechanical energy (i.e., mild stirring/ultrasonication) was applied during the synthesis. Typically, all reactants used here were consistent with those used during the synthesis of SC-HSN; however, CdSe@ ZnS quantum dot (30 μL) was dispered in CTAB-containing aqueous solution, and pyrene (4.5 mg) was dissolved in a mixture of nhexadecane (50 μL) and n-octane (350 μL). The reaction mixture was first stirred at 300 rpm for 5 min and then sonicated in the absence of mechanical stirring for another 15 min. The reduced stirring rate could assist the formation of large SC-HSN, allowing easy microscopic observations. In a similar manner, incorporation of hydrophobic magnetite nanocrystals into SC-HSN (Fe3O4@SC-HSN) was achieved by changing n-octane to magnetite-containing n-octane (31.5 mg mL−1). 2.5. Synthesis of Multiple-Compartment Hollow Silica Nanospheres (MC-HSN). To obtain a high yield of MC-HSN, a formulation consisting of a 227000/1/132/6.9/87.8/19.1 molar ratio of H2O/CTAB/TEOS/C16/C8/C6OH was used. Compared with the formulation for SC-HSN, octane, and hexanol were added. Typically, the reaction procedure and particle-collecting process were the same as those of SC-HSN except an additional 75 μL of n-hexanol was added to the aforementioned oil-phase. 2.6. Incorporation of Nonionic Surfactants in the Synthesis of SC-HSN. Typically, the reaction procedure and particle-collecting process were the same as those of SC-HSN except an additional 75 μL

of nonionic surfactant (CO-520, Triton X-100, or Brij98) was added to the aforementioned oil-phase in three separate experiments. 2.7. Synthesis of Ultrasmall Hollow Silica Nanospheres (USHSN). To obtain US-HSN, a formulation consisting of H2O/CTAB/ TEOS/C16/C8 with a 28405/1/16.5/0.86/11 molar ratio was used. Notice that a much larger amount of CTAB was used here. Ultrasmall HSN were synthesized under the same conditions as the synthesis of SC-HSN except the amount of CTAB was increased from 9 mg to 72 mg. The product was isolated by centrifugation at 15 000 rpm for 60 min or by using an ultra filtration system (Millipore, XFUF07601, regenerated cellulose membrane with a nominal molecular weight limit (NMWL) of 1000 Da). For dialysis purification, surfactants of the assynthesized US-HSN were removed using a dialysis process described by Urata et al.29 2.8. Synthesis of SC-HSN Encapsulating Hydrophilic Rhodamine B and Hydrophobic Pyrene (RhB/Py@SC-HSN). In a similar way to the synthesis of QD/Py@SC-HSN, the RhB/Py@SCHSN encapsulating small molecules of both hydrophilic Rhodamine B and hydrophobic pyrene was obtained by changing CdSe@ZnS quantum dot to rhodamine B (1 mg). 2.9. In vitro Dye Release Studies of RhB/Py@SC-HSN in Simulated Body Fluid. The 100% release values were determined by the extent of absorption of rhodamine B in aqueous phase and pyrene in oil phase after digestion of RhB/Py@SC-HSN using a mixture of 1 M NaOH and n-octane. To detect the released rhodamine B and pyrene molecules, we used two different methods as follows. 2.9a. Determination of the Amount of Released Rhodamine B. Thirty milligrams of RhB/Py@SC-HSN were dispersed in 10 mL of simulated body fluid (SBF, pH 7.4), and transferred to a dialysis membrane composed of regenerated cellulose with a molecular weight cutoff of 12 000−14 000 Da. The dialysis bag was then dialyzed against 190 mL of SBF and gently stirred at 37 °C. At predefined time 354

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oil. To find this out, we deliberately made micrometer-sized large particles so that each compartment of the SC-HSN could be observed and identified under an optical microscope. It is known that, in a kinetically stable O/W nanoemulsion system, the size of the emulsion droplets depends on the mechanical energy applied in the preparation process.25 In addition, in this case of low surfactant concentration, we found that the diameter of the SC-HSN increased with increasing oil-tosurfactant ratio. As a result, some micrometer-sized SC-HSN were obtained (see Figure S2a in the Supporting Information) by introducing n-octane (C8) in the reactants and reducing the mechanical energy (i.e., applying mild stirring/ultrasonication) during synthesis. In this experiment, the formulation consisted of H2O/CTAB/TEOS/C16/C8 in a 227000/1/132/6.9/87.8 molar ratio; e.g. a mixture of alkanes was used. With this formulation, we obtained some micrometer-sized SC-HSN as shown in Figure 2a. We then labeled the micrometer-sized SC-

intervals, 2.5 mL of the dialysate was withdrawn and an equal volume of fresh SBF was added to the dialysate to maintain the constant volume. The withdrawn samples were analyzed for rhodamine B by a UV−vis spectrophotometer. 2.9b. Determination of the Amount of Released Pyrene. Thirty mg of RhB/Py@SC-HSN were dispersed in 200 mL of SBF with stirring. To extract the released hydrophobic molecule, 20 mL of octane was added to the solution. At predefined time intervals, 0.2 mL of the upper oil layer (octane) was withdrawn and analyzed for pyrene by a UV−vis spectrophotometer. An equal volume of fresh octane was added to the mixture to keep the volume constant. 2.10. Characterization. Transmission electron microscopy (TEM) images were taken on a JEOL JSM-1200 EX II operating at 100 kV. N2 adsorption−desorption isotherms were measured at liquid N2 temperature (−196 °C) on a Micrometerics ASAP 2010 apparatus. The samples were degassed at 100 °C overnight under 10−3 Torr before measurements were taken. The specific surface area of the sample was calculated based on the Brunauer−Emmett−Teller (BET) equation at P/P0 between 0.05 and 0.3. The total pore volume was the adsorbed amount at a P/P0 of 0.99. The pore diameter was calculated from the branch of the adsorption isotherm using a Barrett−Joyner− Halenda (BJH) method. Powder X-ray diffraction (XRD) was performed on a PANalytical’s X’Pert PRO X-ray diffractometer using filtered Cu Kα radiation (λ = 0.154 nm). The absorption spectra were recorded on a Hitachi model U-3310 UV/vis scanning spectrophotometer. Dynamic light scattering (DLS) measurements were performed on a Zetasizer Nano ZS (Malvern, UK). Fluorescent images were obtained on a confocal microscope (TCS SP5, Leica).

3. RESULTS We first used a formulation consisting of H2O/CTAB/TEOS/ C16 in a 227000/1/132/6.9 molar ratio to obtain SC-HSN (single-compartment HSN). The oil phase consisted of TEOS and n-hexadecane, and the aqueous solution was pH-neutral. Transmission electron microscopy (TEM) images in Figure 1a show the as-synthesized SC-HSN with an average outerdiameter of 63 ± 15 nm (Size distribution shown in Figure S1 in the Supporting Information). One can see that the nanospheres are hollow, with a nested sphere-within-sphere interior of different contrasts. There is a middle dark region inbetween the two eccentric spheres. Dynamic light scattering (DLS) data (Figure 1b) shows that SC-HSN have an average hydrodynamic diameter of 98 nm in water, indicating that SCHSN are nonaggregating. After calcination, the interior materials of the SC-HSN (designated as SC-HSN_C and shown in Figure 1c) were removed, and simple HSN, without any nested interior, were obtained (Figure 1c). This indicates that the boundary of the encapsulated internal liquids of SCHSN (as shown in Figure 1a) does not contain silica materials. It is most likely a water/oil interface. The N2 adsorption−desorption isotherms of the assynthesized SC-HSN and calcined SC-HSN_C with type IV isotherm behavior are shown in Figure 1d. The as-synthesized SC-HSN (after evaporation of interior liquid) do not have any mesopores, whereas the calcined SC-HSN_C possess mesopores as the desorption branch indicates. The higher BET surface area of SC-HSN_C (307 m2/g), in comparison with that of the as-synthesized SC-HSN (106 m2/g), is mainly due to the formation of nanopores on the shell after calcination. We can conclude that, in the desorption isotherm of SC-HSN_C, the delayed capillary evaporation is due to the formation of large internal voids enclosed by mesopores on the shell.30 In the SC-HSN, although the TEM images showed an internal eccentric double spherical distribution of liquids, it was not clear at first which compartment was water and which was

Figure 2. (a−c) Confocal microscope images of QD/Py@SC-HSN: (a) bright field image; (b) image taken in red-emission channel; (c) image taken in blue-emission channel. (d) TEM image of Fe3O4@SCHSN.

HSN with hydrophilic CdSe@ZnS quantum dots and hydrophobic pyrene molecules (designated as QD/Py@SC-HSN) so that they could be located under a confocal fluorescence microscope. They were synthesized by means of simple encapsulation during the formation process of SC-HSN. The TEM image shows that there was no obvious change in the morphology of SC-HSN after introducing pyrene and QD (see Figure S2b in the Supporting Information). In Figure 2b, the hydrophilic quantum dots (red) are located within the inner spherical region and in the outer continuous aqueous phase. This means the region of the inner sphere was a water phase. On the other hand, Figure 2c shows that the blue fluorescence of the hydrophobic pyrene stayed in the middle region between the two eccentric spheres. Thus, the SC-HSN were derived from a W/O/W double emulsion followed by silica condensation on the outer surface. They were of the water-in-oil-in-silica-in-water (W/O/Silica/W) type. Hence, in 355

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Figure 3. TEM images of (a, d, g, j) as-synthesized and (b, e, h, k) calcined nanoparticles. (c, f, i, l) N2 adsorption−desorption isotherms of the corresponding calcined nanoparticles. (a−c) MC-HSN, HLBmix = 6.52; (d−f) SNP-CO520, HLBmix = 10.0; (g−i) SNP-TritonX100, HLBmix = 13.1; (j−l) SNP-Brij98, HLBmix = 14.8.

double-shelled Cu2O32 and silica33 by templating double nanoemulsions. Here, we have for the first time synthesized silica nanospheres enclosing a water-in-oil droplet, e.g., a singleshelled silica with two nonmixing liquid components inside. Moreover, this method could also be extended to prepare HSN

the TEM images, the dark middle region of the SC-HSN can be identified as the oil phase. This kind of nanosized W/O/W structure (under 100 nm in size) has rarely been observed. A recent example is a W/O/W emulsion prepared from diblock copeptide.31 Previously, there have been reports of synthesizing 356

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nitrogen has the largest hysteresis in desorption due to the strong confinement of the spheres-within-sphere structure of MC-HSN_C as shown in Figure 3b. In comparison, the adsorbed nitrogen can desorb more easily because of the presence of a mesoporous shell on the hollow SNP-Brij98_C as shown in Figure 3k. In addition, for SNP-TritonX100_C with broken hemispheres and mesoporous shells (Figure 3h), the hysteresis in nitrogen adsorption almost disappeared. The pore size distribution calculated from the adsorption branch of SNPTritonX100_C and SNP-Brij98_C shows average pore diameters at 3.8 and 3.5 nm, respectively, which can be attributed to the mesoporous shell observed by TEM. Moreover, the small-angle XRD patterns of SNP-TritonX100_C and SNP-Brij98_C show one broad diffraction peak, suggesting the presence of disordered mesostructures (see Figure S4 in the Supporting Information). Detailed N2 sorption results of these silica nanoparticles are summarized in Table 1.

encapsulating different components. For example, Fe3O4containing SC-HSN could be obtained (designated as Fe3O4@SC-HSN) simply by adding hydrophobic nanomagnetites to the oil-phase at the initial stage of synthesis. A representative TEM image of Fe3O4@SC-HSN is shown in Figure 2d. As expected, we found Fe3O4 nanoparticles located in the middle oil-phase of SC-HSN. The above results indicate that the system is versatile enough for coloading of polar and nonpolar nanocargo. Next, we show that multiple silica nanospheres can be encapsulated within a single larger hollow silica nanosphere to obtain multiple-compartment HSN (MC-HSN). Introducing nhexanol (C6OH) and n-octane in the synthesis mixture could help stabilize the nanoemulsion, yielding hollow particles encapsulating multiple hollow spheres (Figure 3a and Figure S3 in the Supporting Information). Here, the formulation consisted of H2O/CTAB/TEOS/C16/C8/C6OH with a molar ratio of 227000/1/132/6.9/87.8/19.1. From the distribution of the darkness contrast in the TEM picture in Figure 3a, it is inferred that in MC-HSN the internal space of the inner hollow spheres is filled with water, whereas the space between the inner spheres and the outer spheres are filled with oil. It might happen that n-hexanol could serve as a cosurfactant stabilizer and be capable of preventing coalescence of internal water droplets (inside the larger outer sphere). Thus silica condensation also occurred at the encapsulated water/oil interface inside, and W/Silica/O/Silica/W type nanospheres could be formed. After calcination, one obtains silica sphereswithin-sphere as shown in Figure 3b. To investigate the effect of hydrophilic−lipophilic balance (HLB), three other nonionic surfactants including CO-520, Triton X-100, and Brij98, with increasing HLB values, were used to replace n-hexanol in synthesis (HLBC6OH = 6.00; HLBCO‑520 = 10.0; HLBTritonX‑100 = 13.5; HLBBrij98 = 15.3). (A lower HLB value corresponds to a more hydrophobic molecule, and a higher HLB value corresponds to a more hydrophilic molecule.) Figure 3d, g, and j shows the corresponding TEM images of the as-synthesized HSN. The resulting silica nanoparticles (SNP) were distinctly different from MC-HSN both in structure and morphology. Using Brij98 in the synthesis, the obtained nanospheres are simple hollow spheres (Figure 3j) with even silica shell thickness (designed as SNPBrij98). This structure is typical hollow particles synthesized via O/W microemulsion (or expanded micelle) templating approach.34 Using CO-520 in the synthesis, the obtained HSN is a porous nanosphere (Figure 3d) with a large bicontinuous interior structure and mesopores on its surface (designed as SNP-CO520). Particles with similar structure can be found in a previous report,35 where both styrene monomer and CTAB were used as templates and the synthesis involved simultaneous hydrolytic condensation of TEOS to form silica and polymerization of styrene into polystyrene. With Triton X100 in the synthesis, the obtained SNP is a mixture of hollow silica nanosphere and sphere-within-hemisphere (Figure 3g) with uneven shell thickness (designed as SNP-TritonX100). All N2 sorption isotherms of these calcined silica nanoparticles (designed as SNP-surfactant_C), exhibit Type IV isotherms with a hysteresis loop. As shown in Figure 3c, f, i, and l, a significantly increasing trend of the extent of hysteresis can be found from SNP-TritonX100_C to SNP-CO520_C, to SNPBrij98_C, to MC-HSN_C. The results of nitrogen adsorption isotherms can be interpreted with the TEM observations on particle morphology, structure and pore size. The adsorbed

Table 1. Textual Properties of the Silica Nanoparticles Prepared via Nanoemulsion-Templating Route sample

SBETa (m2/g)

Vtb (cm3/g)

DBJHc (nm)

SC-HSN SC-HSN_C MC-HSN_C SNP-CO520_C SNP-TritonX100_C SNP-Brij98_C US-HSN_D

106 307 325 452 440 484 312

0.76 0.99 1.73 2.03 1.26 0.96 0.36

ND ND ND ND 3.8 3.5 3.3

a

SBET, specific surface area calculated based on the Brunauer− Emmett−Teller (BET) equation at P/P0 between 0.05 and 0.3. bVt, total pore volume calculated at P/P0 = 0.99. cDBJH, pore diameter assigned from the maximum of the pore size distribution calculated from the BJH method.

For possible applications in drug delivery, the alkane employed needs to be replaced by more biocompatible oils. For this purpose, biocompatible products of HSN were synthesized in similar processes by substituting the n-alkanes with various vegetable oils, including (a) soybean, (b) sunflower, (c) peanut, (d) olive, (e) coconut, and (f) corn oil. As shown in Figure 4, all the particles are still in the form of compartmentalized HSN to various extents. Most of the HSN are less uniform than those shown in Figure 1. The HSN materials made from vegetable oils substantiate the potential for applying this type of material in food and pharmaceutical industries. We will discuss the process later in the discussion. Next, we investigated the effect of increasing the amount of surfactant CTAB in the synthesis mixture of H2O/CTAB/ TEOS/C16/C8. When the amount of CTAB used in the reaction was increased to 6 times that used in the preparation of MC-HSN, many well-separated ultrasmall hollow silica nanospheres (US-HSN) were observed in the product. The solution became transparent and very well-suspended. With the further increase of CTAB, the yield of US-HSN gradually increased up to 95% when 8-fold CTAB was used (Figure 5a; the molar ratio of H2O/CTAB/TEOS/C16/C8 was 28405/1/16.5/0.86/11). The average diameter of the US-HSN was 12 nm with a very narrow size distribution (8%, as shown in Figure S5 in the Supporting Information). Because the US-HSN structures are mostly broken after calcination, we used dialysis to remove surfactant. Nitrogen sorption isotherm and the BJH pore size 357

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Figure 4. TEM images of as-prepared compartmentalized HSN synthesized using (a) soybean, (b) sunflower, (c) peanut, (d) olive, (e) coconut, and (f) corn oil as the oil phase.

Figure 5. (a) TEM images (enlarged in inset) of US-HSN; (b) N2 adsorption−desorption isotherms and BJH pore size distribution curve (inset) of US-HSN_D; (c) hydrodynamic diameter distributions and (d) zeta potentials of US-HSN and US-HSN_D. (Polydispersity index of both US-HSN and US-HSN_D is 0.40.)

classification,36 which is often a result of pores with narrow mouths (ink-bottle pores) and had also been observed for other hollow structures.37 The BET surface area of US-HSN_D was

distribution curve of US-HSN after dialysis (designed as USHSN_D) are shown in Figure 5b. The isotherm is of Type IV with a Type H2 hysteresis loop according to IUPAC 358

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Figure 6. (a) In vitro release profiles of rhodamine B and pyrene molecules from RhB/Py@SC-HSN in simulated body fluid at 37 °C. Data represent mean ± SD from three independent experiments; (b, c) TEM images of RhB/Py@SC-HSN (b) before and (c) after immersing in simulated body fluid at 37 °C for a week.

312 m2 g−1, which is close to the theoretical surface area using the average diameter of US-HSN_D and its shell-thickness obtained by TEM measurements. It should be noted that, in such hollow spheres possessing an interior diameter of 3−4 nm and an external diameter of 12.2 nm, the surface area is attributed to the shell surface of US-HSN_D.38 Compared to the calcined nanoparticles mentioned above, i.e. SC-HSN_C, MC-HSN_C and SNP-surfactant_C, the small amount of textural adsorption appearing at high relative pressure (P/P0 > 0.9) implies that the packing of the dried US-HSN_D is tight, and the interstitial space between US-HSN_D is similar to the internal pore size.37b The pore size distribution calculated from the adsorption branch of the nitrogen isotherm by the BJH method indicates a mesopore peak with a diameter of 3.3 nm. Previously, Tatsumi and co-workers reported solid silica nanospheres with a diameter of 12 nm and a well-ordered packing.39 It is particularly noteworthy that both the N2 sorption isotherm and BJH pore size distribution between Tatsumi’s solid silica nanospheres and the hollow silica nanospheres (US-HSN_D) reported here are very similar. In their research, they have demonstrated that the uniform mesopores were attributed to the interstitial space between uniform solid silica nanospheres, which can assemble into tightly packed 3D structures.39,40 Dynamic light scattering measurements revealed as-synthesized US-HSN with a zeta potential of +33 mV and an average hydrodynamic diameter of 24 nm (Figure 5c, d). This means that the silicate’s negative charges were not strong enough to compensate for the positive charge of CTAB, and that the positively charged hollow spheres repulsed each other to prevent the formation of liquid crystalline phase. It is noted that under the synthesis condition (neutral pH and ultrasonication), the surfactant CTAB and TEOS did not form bulk mesoporous silica MCM-41 materials. Instead, a transparent suspension of ultrasmall US-HSN was obtained because of the electrostatic repulsion between the silica-encapsulated micelles. Finally, we explore the potential application in codelivery of drugs with the material SC-HSN that can simultaneously encapsulate nonpolar liquid and water inside hollow silica sphere. Thus, one can expect a codelivery of two different agents, one of hydrophobic and another one of hydrophilic nature. Here, rhodamine B as a model hydrophilic compound and pyrene as a model hydrophobic compound were incorporated simultaneously into the SC-HSN (designated as

RhB/Py@SC-HSN). A TEM picture of RhB/Py@SC-HSN is shown in Figure 6b. In vitro dye release studies of RhB/Py@ SC-HSN were performed in simulated body fluid (SBF, pH 7.4) at 37 °C. As shown in Figure 6a, the cumulative amount of dye released in 48 h reached 90% for pyrene, and 80% for rhodamine B. It is noteworthy that both the release kinetics of hydrophobic pyrene and hydrophilic rhodamine B from the RhB/Py@SC-HSN are similar to the degradation behavior of amorphous silica reported by Shi and co-workers.41 In addition, TEM observation showed the morphology of RhB/Py@SCHSN changed from SC-HSN into broken HSN without interior W/O droplet after immersed in stirred SBF at 37 °C for a week (Figure 6b, c). Therefore, it can be concluded that the dyes release mechanism was predominantly controlled by silica dissolution.41,42

4. DISCUSSION In the last section, we have presented the syntheses and characterizations of silica templated by nanoemulsions. A rich variety of nested hollow silica spheres are observed. The physicochemical mechanism in influencing their structures would be highly interesting to investigate. Here, we give some initial propositions on mechanism and the physical chemistry involved in this new materials. Sonochemistry and Hydrolysis of TEOS. There are two important considerations in templating nanoemulsions with silica: (a) fast hydrolysis and (b) fast silica condensation, in order to capture and solidify the nonequilibrium nanoemulsion organization. However, these two requirements are normally mutually exclusive under the neutral pH condition within which we are working. In normal sol−gel synthesis using TEOS, without sono-excitation, the hydrolysis of TEOS needs either acid or base catalysts. At neutral pH, the hydrolysis of TEOS is relatively slow although the silica condensation reaction will be fast. Fortunately, TEOS can be hydrolyzed under sonochemical excitation.43 Ultrasonic irradiation, instead of commonly used basic or acidic catalyst, was used to produce acoustical cavitation within the liquid H2O/TEOS reactants. The ultrasonic cavitation produces hydrolyzed silicate species under pH-neutral catalyst-free condition, according to the following reactions43 H 2O + ultrasound → H • + • OH 359

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TEM images of the as-prepared products using various food oils. The viscosities of the food oils are at least 10 times higher than that of hexadecane and 2 orders of magnitude higher than octane. Thus one can see many tiny HSN at about 20 nm in every case in Figure 4. However, probably the very small nanoemulsions formed in food oil are not very stable against coalescence, and there are also many large HSN (up to 100 nm). The size distribution of HSN is less uniform in all cases of using food oils. Nonetheless, we still observed many HSN in multicompartment form (see Figure 4d−f). However, for discussing the various internal structures of the HSN, stability of the nanoemulsion is a physicochemical problem one needs to understand first. There are two mechanisms for destabilizing a nanoemulsion: coalescence and Ostwald ripening.15a,b,47 The first mechanism is to reduce the high surface free energy caused by increased oil−water interfacial area. For the double nanoemulsions, there are two types of coalescence: the internal coalescence where the inner water nanodroplets coalesce to form eventually a single internal water pool and the external coalescence where inner water droplet coalesces with the external water phase to release the internal water to continuous water phase. For now, we consider internal coalescence only because the silica condensation on the external shell is fast enough to prevent external coalescence. In the initial stage of ultrasonication, multiple emulsions with multiple inner W/O droplets (mW/O/W) were formed. Then during intense ultrasonication, TEOS was extensively hydrolyzed to form silicate species. Under neutral conditions, the silica condensation rate is fast. Thus, silica condensation at the interfaces competed with the internal coalescence of W/O/W. If the rate of silica condensation on the inner water/oil interface was faster than that of internal coalescence, mW/O/W was obtained (W/Silica/O/Silica/W) and one would obtain MCHSN. On the other hand, if the encapsulated nanodroplets were not well-protected by surfactants, they would quickly coalesce to form a single encapsulated oil-in-water droplet while silica condensation could still form the outer silica shell in SCHSN. Role of Hexanol. It appears that n-hexanol is crucial for stabilizing the multiple inner nanospheres long enough for silica encapsulation to occur. Without hexanol, the solubility of surfactant in the encapsulated oil phase is low and water droplets are not protected, and SC-HSN (W/O/Silica/W) were obtained after the coalescence of multiple inner droplets into a single droplet. On the other hand, when hexanol is used, it is dissolved in the oil phase and makes the solubility of surfactant in the encapsulated oil phase a lot higher. The water nanodroplet can be quickly protected by adsorbed CTAB and the film between two colliding water nanodroplets is stable (Gibbs-Marangoni effect). This seems to stabilize the thermodynamically unstable multiple emulsions just long enough for silica condensation to “fix” the stable MC-HSN. The ultrasound-induced silica hydrolysis/condensation in forming mesoporous silica helps in fixing rapidly the soft structure.48 Hexanol also could be distributed at the water−oil interface as a cosurfactant. The cosurfactant n-hexanol has been employed in other studies to decrease the water/oil interfacial tension and to assist in the formation of more stable nanoemulsion systems. It may play a similar role of cosurfactant as in some well-known microemulsions. The decreased interfacial tension would probably also help toward multiplenanoemulsion.

(CH3 − CH 2 − O)4 Si + ultrasound → (CH3 − CH 2 − O)3 Si • + • O − CH 2 − CH3 (CH3 − CH 2 − O)3 Si • + • OH → (CH3 − CH 2 − O)3 Si − OH

Under neutral conditions, the condensation of silanol species is rapid and the silica shell can thus be formed in a very short period. The technique of ultrasonic hydrolysis of TEOS has been applied in producing lysozyme-silica hybrid hollow particles44 and coating of magnetite nanoparticles with silica45 under neutral condition. Formation of Multiple Nanoemulsion-Templated Silica Structures. After the sol−gel chemistry of TEOS under sono-excitation is discussed, we would like now to propose the formation mechanism for the structures of SCHSN, MC-HSN and US-HSN. In general, nanoemulsions are formed under strong shearing of oil/water interface and collision of water with oil droplets. Thus, the role of ultrasonication is 2-fold: the creation of silanol species through free radical process as discussed above and providing the strong shearing of the initial oil-in-water macroemulsion. The strong shearing action on oil-in-water droplet would produce long and thin O/W structure which finally breaks up into nanodroplets. Collisions of the nanodroplets with smaller water droplets would produce W/O/W type multiple nanoemulsions. Scheme 2 depicts the mechanism we propose, based on our experimental evidence. The initial mechanical stirring created Scheme 2. Schematic Illustration of the Synthesis and Possible Mechanism for the Transformation of Emulsion from Double Emulsions with Multiple Inner W/O Droplets (mW/O/W, product designed as MC-HSN) to a Single Inner W/O Droplet (sW/O/W, product designed as SCHSN)

an oil-in-water (O/W) macroemulsion. After ultrasonication, the O/W macroemulsion transformed to nanoemulsion along with the formation of W/O/W multiple nanoemulsions. The viscosity of the oil phase would determine the initial size of the nanoemulsion. The formation mechanism of nanodroplet formation in an oil−water system is that through strong shearing, thin strings of oil are formed first before they destabilize to droplets. Given the same input energy, oil of higher viscosity would support stronger thinning before its break-up.46 Indeed, we generally found hexadecane would give smaller HSN than octane did. In Figure 4, we also presented 360

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Scheme 3. Schematic Illustration of the Formation of Hollow Nanoparticles with Bicontinuous Structure in the Interior

Ostwald Ripening. Moreover, in addition to the coalescence process, it is known that another primary instability mechanism of nanoemulsions is Ostwald ripening.25,49 Previously, Kabal’nov et al.50 proposed a method to kinetically suppress Ostwald ripening by exploiting the entropy of mixing two oils. Oil could be trapped in a droplet better with another oil substance because of increased entropy of mixing. It was then shown experimentally that the idea indeed worked for nanoemulsions of mixed alkanes.49b,51 Rather interesting is the case of US-HSN. For the extremely small sized US-HSN, they are highly charged and the electrostatic repulsion between them would prevent coalescence mechanism for destabilization. Ostwald ripening would be the dominant destabilization mechanism because of the large Laplace pressure inside.24 Apparently, at high CTAB content, the O/W droplets with the assistance of binary alkanes (C8+C16) is extremely fine such that they are much more stable and do not coalesce. This is feasible because of the rapid ultrasound induced hydrolysis and condensation under neutral pH conditions. At the same time, the mixed oil of hexadecane and octane helps to suppress Ostwald ripening. Consequently, we can reasonably infer that, in this reaction, the mixed oilexpanded CTAB micelles behaved as stable soft templates in the formation of US-HSN. Previously, Liu et al. created ultrasmall HSN by using surfactant F127 as a template and tetramethoxysilane (TMOS) as a precursor in a buffer solution, but unfortunately the resulting HSN were highly aggregated which would not be very useful in solution applications.52 Factors such as stability and dispersibility of nanoparticles would be important criterions in biomedical applications.53 Our US-HSN possesses the concurrent excellent properties of longterm colloidal stability and extremely small size. The 12 nm external and the 3−4 nm internal size of US-HSN may lead to many new applications and will be the subject of a future study Various Encapsulated Internal Structures. Next, we would like to understand the results in Figure 3 where one obtained HSN with various internal structures by changing the surfactants employed. The surfactants are of different hydrophilic−lipophilic balance and various spontaneous curvatures of the surfactant monolayer would form between oil and water phases. The addition of the cosurfactant hexanol has been known to make the surfactant monolayer flexible and balanced which enables the observation of the classical Winsor I-Winsor III-Winsor II sequence of various spontaneous curvatures for the oil/water interface.54 Griffin first established the hydrophilic−lipophilic balance (HLB) system to classify surfactants, where low HLB values are assigned for lipophilic surfactant (favoring water-in-oil (W/O) curvature) and high HLB values are for hydrophilic surfactants (favoring oil-in-water (O/W) curvature). Because we have the cosurfactant hexanol (HLBhexanol = 6.00), the HLB number for a mixture of surfactants in each aforementioned condition was calculated by

averaging over the weight fraction composition of the mixture (see the Supporting Information). We have thus the values for HLBmix = 6.52 for the cases of hexanol (Figure 3a−c), HLBmix = 10.0 for CO-520 (Figure 3d−f), HLBmix = 13.1 for Triton X100 (Figure 3g−i), and HLBmix = 14.8 for Brij98 (Figure 3j−l). In a typical double emulsion situation, there are two interfaces of opposite curvatures. The standard method of preparation W/O/W double emulsion involves two-step and two surfactants of different HLB values in order to create the two opposite curvatures.55 In rare situations, only one block copolymer surfactant was used to create a W/O/W double emulsion where two different conformations of the block copolymer apparently existed on the O/W and W/O interfaces.56 In our synthesis, only one step was carried out in each case. We were able to create a multiple-emulsion because of the extra silicates adsorbed on the O/W interface in the initial stage. The ionic interaction of silicate makes the surfactant on O/W interface more hydrophilic and stabilizes the outer O/W interface. For the case of Figure 3a, the low HLB value of the hexanol/CTAB system stabilized the inner W/O interface while the outer O/W interface was stabilized by the hexanol/CTAB/ silicate combination. Thus one can have a stable multiple nanoemulsion system in the initial stage. Later on, further silica condensation produced the silica shell for both interfaces (see Figure S3 in the Supporting Information). In the other limiting case of Figure 3j where Brij98 with high HLB value was used, the high HLB situation made the inner interface unstable and internal coalescence led to a SC-HSN product just like the situation of Figure 1a. The two cases of intermediate HLB value (CO-520 and Triton X-100) are rather interesting in that two different encapsulated inner structures were obtained. Again, the results of Figure 3d, g can be rationalized by the HLB systems. The HLB value of the CO-520 system is higher than that of the hexanol system but lower than the HLB value of Triton X-100 system (Figure 3g). Thus the CO-520 system favors a W/O interfacial curvature between those of Figure 3a (sphere) and Figure 3g (nearly flat) that is bicontinuous (Figure 3d). A schematic description of the bicontinuous interior structure is given in Scheme 3. To understand the bicontinuous interior structure, we used another nonionic surfactant polyethylene-block-poly(ethylene glycol) (PE-bPEG), with the same HLB value as that of CO-520 (HLB = 10) but having higher molecular weight (Mn ≈ 920) than that of CO-520 (Mn∼441), to replace CO-520 in the synthesis. As shown in Figure S6 in the Supporting Information, the obtained silica nanoparticles are smaller but with similar bicontinuous structure as those formed with CO-520. It seems HLB value of amphiphile indeed determines the curvature of the interior structure but other factors such as molecular weight could influence the size of the HSN. 361

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biocompatible for future in vivo applications. For the case of coconut oil@SC-HSN, we have performed a simple cellviability assay of HeLa cells treated with 100 μg/mL of RhB/ Coconut oil@SC-HSN. The results gave nearly 100% cell viability. (For details, see Figure S7 in the Supporting Information) However, more detailed studies of the biocompability of our HSN would be desirable in the future.

The case of Triton X-100 is most interesting (Figure 3g) where many outer shells were apparently only partially formed where inner spheres or hemispheres were encapsulated. We believe the inner spheres have rather unstable curved interface due to the high HLB value here, flat interfacial curvature is more favored such that external coalescence occurred to relieve the poor energy situation. External coalescence has been known to occur when the hydrophilic surfactant favors a change of W/ O interfacial curvature when it is in contact with the external surface producing an opening and release the inner water droplet to the continuous water phase.57 The external coalescence in Figure 3g was only partial, apparently because it was in competition with the silica condensation of the external shell. Many of the outer shells in Figure 3g might have been too rigid to allow external coalescence. Previously, we have synthesized HSN using microemulsions as templates of either the oil-in-water (O/W)58 or water-in-oil (W/O)3a,8a,b type. We would like to make a brief comparison of the advantage and disadvantage of the nanoemulsion template developed in this work with respect to our previous microemulsion approach. An important advantage of the nanoemulsion method over the microemulsion method is the lower surfactant concentration required for their formation. Except for US-HSN, the concentration of surfactants used in this work is less than critical micelle concentration. Because of this, the mesopores on the silica shell in this work are generally less than those obtained using microemulsion method. Second, as we have explained, the nanoemulsion approach allows a synthesis of HSN under neutral pH condition, whereas in the microemulsion-templated approach, base- or acid-catalyzed hydrolysis of TEOS is needed. Most importantly, in nanoemulsion approach, nested multiple emulsion structures could be easily obtained for many oils and surfactants. The choices of oil type and surfactants are more flexible. For microemulsion, because it is a thermodynamic equilibrium system, the choices of oil and surfactants are much more stringent while we have not been able to obtain a multiple microemulsion system for the silica templating. Also, nanoemulsions generally possess higher stability against sedimentation and flocculation. On the other hand, the HSN from microemulsion approaches are generally more uniform in size because microemulsion droplets are thermodynamic equilibrium structures. Also, encapsulation of nanoparticles (such as gold) within HSN from the microemulsion method seems to be easier, whereas we have not been able to encapsulate foreign nanoparticles in our SCHSN or MC-HSN in a precisely controllable way. Finally, our material of HSN encapsulating a single W/O droplet (SC-HSN) and our multiple HSN encapsulated in a hollow silica nanoparticle (MC-HSN) are the first examples of complex hollow silica structures templated by nanoemulsion. We point out that nanoemulsion templating is a rather robust technique with which many different surfactants and solution components can be used as we have demonstrated here. In contrast, the microemulsion-templating (or micelle-templating) method would be much more specific to the surfactant used because it is a nearly equilibrium system and thus sensitive to solution and surfactant composition. A compromise is that nanoemulsion systems usually gives more polydisperse size and shape distribution because they are agitated rigorously and in highly nonequilibrium condition. Complex fluid dynamics are in play and it is difficult to control the final size and shape. However, as we have shown that many edible oils may be used in the initial o/w template in our nanoemulsion, they would be

5. CONCLUSIONS In summary, a nanoemulsion-templating approach has been demonstrated for the synthesis of silica nanoparticles with compartmentalized hollow structure via ultrasound-assisted sol−gel method. A mechanism involving transformation of the nanoemulsion and the effect of surfactant on particle structure, size, as well as morphology is proposed. Compartmentalization is one of the key features of biological organizations; for example, cells are compartmentalized by different organelles such as endosomes, ribosomes etc. The biomimetics of compartmentalized self-assembly have received a lot of attention with the building of polymersomes, which are vesicles that can be made from synthetic or biological polymers.59 In contrast, there have been very few examples of multiplecompartment hollow inorganic nanoparticles. To the best of our knowledge, the material SC-HSN mentioned here is the first report on the synthesis of a HSN with a W/O droplet inside. In addition, an intriguing application of SC-HSN for codelivery of oil-soluble and water-soluble dyes was demonstrated in simulated body fluid (SBF) by a dissolutioncontrolled mechanism.41,42 It would be of great interest to find biomedical applications of these materials, for example, as a multifunctional drug delivery vehicle.60 Another potential application would be using MC-HSN or porous HSN to confine nanocatalysts for selective catalysis.13,61 Moreover, it is believed that the US-HSN, with a uniform diameter of 12 nm and a cavity diameter of 3.3 nm, will be able to provide a platform for advancing scientific research, such as research on the physicochemical behavior of water in 3D confined space.62



ASSOCIATED CONTENT

S Supporting Information *

Size distribution histograms of SC-HSN and US-HSN. TEM images of large SC-HSN, QD/Py@SC-HSN, as-synthesized MC-HSN, SNP-PE-b-PEG, and RhB/Coconut oil@SC-HSN. Small-angle XRD patterns of SC-HSN_C, MC-HSN_C, SNPCO520_C, SNP-TritonX100_C, SNP-Brij98_C, and USHSN_D. Calculation of the HLB number from a mixture of surfactants. Cell viability assay.This material is available free of charge via the Internet at http://pubs.acs.org.



AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Fax: +886-2-23660954. Tel: +886-2-33665251. Notes

The authors declare no competing financial interest.



ACKNOWLEDGMENTS The authors thank the National Project of Nanotechnology under the National Science Council of Taiwan for the support of their research. 362

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S. F.; Price, A. D.; Stadler, B.; Caruso, F. Nano Lett. 2011, 11, 4958− 4963. (20) (a) Kreft, O.; Prevot, M.; Mohwald, H.; Sukhorukov, G. B. Angew. Chem., Int. Ed. 2007, 46, 5605−5608. (b) Baumler, H.; Georgieva, R. Biomacromolecules 2010, 11, 1480−1487. (21) Shum, H. C.; Zhao, Y.-j.; Kim, S.-H.; Weitz, D. A. Angew. Chem., Int. Ed. 2011, 50, 1648−1651. (22) Chandrawati, R.; Hosta-Rigau, L.; Vanderstraaten, D.; Lokuliyana, S. A.; Stadler, B.; Albericio, F.; Caruso, F. ACS Nano 2010, 4, 1351−1361. (23) (a) Tadros, T.; Izquierdo, P.; Esquena, J.; Solans, C. Adv. Colloid Interface Sci. 2004, 108−109, 303−318. (b) Solans, C.; Izquierdo, P.; Nolla, J.; Azemar, N.; Garcia-Celma, M. J. Curr. Opin. Colloid Interface Sci. 2005, 10, 102−110. (c) McClements, D. J. Soft Matter 2012, 8, 1719−1729. (24) Delmas, T.; Piraux, H.; Couffin, A. C.; Texier, I.; Vinet, F.; Poulin, P.; Cates, M. E.; Bibette, J. Langmuir 2011, 27, 1683−1692. (25) (a) Fryd, M. M.; Mason, T. G. Annu. Rev. Phys. Chem. 2012, 63, 493−518. (b) Koroleva, M. Y.; Yurtov, E. V. Russ Chem Rev+ 2012, 81, 21−43. (c) Wilking, J. N.; Chang, C. B.; Fryd, M. M.; Porcar, L.; Mason, T. G. Langmuir 2011, 27, 5204−5210. (d) Mason, T. G.; Wilking, J. N.; Meleson, K.; Chang, C. B.; Graves, S. M. J. Phys.: Condens. Matter 2006, 18, R635−R666. (26) (a) Peng, B.; Chen, M.; Zhou, S.; Wu, L.; Ma, X. J. Colloid Interface Sci. 2008, 321, 67−73. (b) Schiller, R.; Weiss, C. K.; Geserick, J.; Husing, N.; Landfester, K. Chem. Mater. 2009, 21, 5088−5098. (27) Kokubo, T.; Kushitani, H.; Sakka, S.; Kitsugi, T.; Yamamuro, T. J. Biomed. Mater. Res. 1990, 24, 721−734. (28) Sun, S.; Zeng, H. J. Am. Chem. Soc. 2002, 124, 8204−8205. (29) Urata, C.; Aoyama, Y.; Tonegawa, A.; Yamauchi, Y.; Kuroda, K. Chem. Commun. 2009, 5094−5096. (30) (a) Groen, J. C.; Peffer, L. A. A.; Perez-Ramirez, J. Micro. Meso. Mater. 2003, 60, 1−17. (b) Thommes, M.; Smarsly, B.; Groenewolt, M.; Ravikovitch, P. I.; Neimark, A. V. Langmuir 2005, 22, 756−764. (31) Hanson, J. A.; Chang, C. B.; Graves, S. M.; Li, Z.; Mason, T. G.; Deming, T. J. Nature 2008, 455, 85−88. (32) Xu, H.; Wang, W. Angew. Chem., Int. Ed. 2007, 46, 1489−1492. (33) Zhao, Y.; Zhang, J.; Wang, Q.; Li, J.; Han, B. Phys. Chem. Chem. Phys. 2011, 13, 684−689. (34) (a) Wang, J. G.; Li, F.; Zhou, H. J.; Sun, P. C.; Ding, D. T.; Chen, T. H. Chem. Mater. 2009, 21, 612−620. (b) Mandal, M.; Kruk, M. Chem. Mater. 2012, 24, 123−132. (35) Nandiyanto, A. B. D.; Kim, S. G.; Iskandar, F.; Okuyama, K. Micro. Meso. Mater. 2009, 120, 447−453. (36) Sing, K. S. W.; Everett, D. H.; Haul, R. A. W.; Moscou, L.; Pierotti, R. A.; Rouquerol, J.; Siemieniewska, T. Pure Appl. Chem. 1985, 57, 603−619. (37) (a) Li, X. B.; Liu, X.; Ma, Y.; Li, M. R.; Zhao, J.; Xin, H. C.; Zhang, L.; Yang, Y.; Li, C.; Yang, Q. H. Adv. Mater. 2012, 24, 1424− 1428. (b) Tang, J. W.; Zhou, X. F.; Zhao, D. Y.; Lu, G. Q.; Zou, J.; Yu, C. Z. J. Am. Chem. Soc. 2007, 129, 9044−9048. (c) Qi, G. G.; Wang, Y. B.; Estevez, L.; Switzer, A. K.; Duan, X. N.; Yang, X. F.; Giannelis, E. P. Chem. Mater. 2010, 22, 2693−2695. (38) Watanabe, R.; Yokoi, T.; Kobayashi, E.; Otsuka, Y.; Shimojima, A.; Okubo, T.; Tatsumi, T. J. Colloid Interface Sci. 2011, 360, 1−7. (39) Yokoi, T.; Sakamoto, Y.; Terasaki, O.; Kubota, Y.; Okubo, T.; Tatsumi, T. J. Am. Chem. Soc. 2006, 128, 13664−13665. (40) Wang, J. Z.; Sugawara-Narutaki, A.; Fukao, M.; Yokoi, T.; Shimojima, A.; Okubo, T. ACS Appl. Mater. Interface 2011, 3, 1538− 1544. (41) He, Q. J.; Shi, J. L.; Zhu, M.; Chen, Y.; Chen, F. Microporous Mesoporous Mater. 2010, 131, 314−320. (42) (a) Lin, Y. S.; Abadeer, N.; Hurley, K. R.; Haynes, C. L. J. Am. Chem. Soc. 2011, 133, 20444−20457. (b) Ehrlich, H.; Demadis, K. D.; Pokrovsky, O. S.; Koutsoukos, P. G. Chem. Rev. 2010, 110, 4656− 4689. (43) Ocotlan-Flores, J.; Saniger, J. M. J. Sol−Gel Sci. Technol. 2006, 39, 235−240.

REFERENCES

(1) (a) Zhu, J.; Tang, J.; Zhao, L.; Zhou, X.; Wang, Y.; Yu, C. Small 2010, 6, 276−282. (b) Tan, H.; Liu, N. S.; He, B.; Wong, S. Y.; Chen, Z.-K.; Li, X.; Wang, J. Chem. Commun. 2009, 6240−6242. (c) Liu, J.; Fan, F.; Feng, Z.; Zhang, L.; Bai, S.; Yang, Q.; Li, C. J. Phys. Chem. C 2008, 112, 16445−16451. (d) Gao, J.; Liu, J.; Bai, S.; Wang, P.; Zhong, H.; Yang, Q.; Li, C. J. Mater. Chem. 2009, 19, 8580−8588. (2) (a) Yeh, Y.-Q.; Chen, B.-C.; Lin, H.-P.; Tang, C.-Y. Langmuir 2005, 22, 6−9. (b) Boyer, C.; Zasadzinski, J. A. ACS Nano 2007, 1, 176−182. (c) Liu, J.; Hartono, S. B.; Jin, Y. G.; Li, Z.; Lu, G. Q.; Qiao, S. Z. J. Mater. Chem. 2010, 20, 4595−4601. (d) Li, H.; Liu, J.; Xie, S. H.; Qiao, M. H.; Dai, W. L.; Lu, Y. F.; Li, H. X. Adv. Funct. Mater. 2008, 18, 3235−3241. (3) (a) Lin, Y.-S.; Wu, S.-H.; Tseng, C.-T.; Hung, Y.; Chang, C.; Mou, C.-Y. Chem. Commun. 2009, 3542−3544. (b) Zoldesi, C. I.; Imhof, A. Adv. Mater. 2005, 17, 924−928. (c) Teng, Z.; Han, Y.; Li, J.; Yan, F.; Yang, W. Micro. Meso. Mater. 2010, 127, 67−72. (d) Ciriminna, R.; Sciortino, M.; Alonzo, G.; Schrijver, A. d.; Pagliaro, M. Chem. Rev. 2010, 111, 765−789. (e) Schmidt-Winkel, P.; Lukens, W. W.; Yang, P.; Margolese, D. I.; Lettow, J. S.; Ying, J. Y.; Stucky, G. D. Chem. Mater. 2000, 12, 686−696. (4) Lin, H.-P.; Mou, C.-Y. Acc. Chem. Res. 2002, 35, 927−935. (5) Lu, G. Q.; ZhaoX. S. Nanoporous Materials: Science and Engineering; Imperial College Press: London, 2004. (6) (a) Zhao, Y.; Jiang, L. Adv. Mater. 2009, 21, 3621−3638. (b) Zeng, H. C. J. Mater. Chem. 2011, 21, 7511−7526. (c) Wang, M.; Chen, C.; Ma, J. P.; Zheng, X.; Li, Q. W.; Jin, Y. Q.; Xu, J. J. Mater. Chem. 2012, 22, 11904−11907. (7) (a) Zhao, Y.; Lin, L.-N.; Lu, Y.; Chen, S.-F.; Dong, L.; Yu, S.-H. Adv. Mater. 2010, 22, 5255−5259. (b) Chen, Y.; Chen, H.; Ma, M.; Chen, F.; Guo, L.; Zhang, L.; Shi, J. J. Mater. Chem. 2011, 21, 5290− 5298. (8) (a) Wu, S.-H.; Tseng, C.-T.; Lin, Y.-S.; Lin, C.-H.; Hung, Y.; Mou, C.-Y. J. Mater. Chem. 2011, 21, 789−794. (b) Lin, C.-H.; Liu, X.; Wu, S.-H.; Liu, K.-H.; Mou, C.-Y. J. Phys. Chem. Lett. 2011, 2, 2984− 2988. (c) Li, J. A.; Liu, J.; Wang, D. H.; Guo, R. S.; Li, X. L.; Qi, W. Langmuir 2010, 26, 12267−12272. (9) Xu, L. G.; He, J. H. Langmuir 2012, 28, 7512−7518. (10) Chen, M.; Wu, L. M.; Zhou, S. X.; You, B. Adv. Mater. 2006, 18, 801−806. (11) (a) Li, W. J.; Sha, X. X.; Dong, W. J.; Wang, Z. C. Chem. Commun. 2002, 2434−2435. (b) Hah, H. J.; Kim, J. S.; Jeon, B. J.; Koo, S. M.; Lee, Y. E. Chem. Commun. 2003, 1712−1713. (12) Park, J. N.; Forman, A. J.; Tang, W.; Cheng, J. H.; Hu, Y. S.; Lin, H. F.; McFarland, E. W. Small 2008, 4, 1694−1697. (13) (a) Lee, C. H.; Lin, T. S.; Mou, C. Y. Nano Today 2009, 4, 165− 179. (b) Jin, D.; Park, K. W.; Lee, J. H.; Song, K.; Kim, J. G.; Seo, M. L.; Jung, J. H. J. Mater. Chem. 2011, 21, 3641−3645. (14) Muschiolik, G. Curr. Opin. Colloid Interface Sci. 2007, 12, 213− 220. (15) (a) Ficheux, M. F.; Bonakdar, L.; Leal-Calderon, F.; Bibette, J. Langmuir 1998, 14, 2702−2706. (b) Pays, K.; Giermanska-Kahn, J.; Pouligny, B.; Bibette, J.; Leal-Calderon, F. Langmuir 2001, 17, 7758− 7769. (c) Gao, F.; Su, Z.-G.; Wang, P.; Ma, G.-H. Langmuir 2009, 25, 3832−3838. (d) Sideratou, Z.; Sterioti, N.; Tsiourvas, D.; Paleos, C. M. ChemPhysChem 2009, 10, 3083−3089. (16) (a) Groschel, A. H.; Schacher, F. H.; Schmalz, H.; Borisov, O. V.; Zhulina, E. B.; Walther, A.; Muller, A. H. E. Nat Commun 2012, 3. (b) Groschel, A. H.; Walther, A.; Lobling, T. I.; Schmelz, J.; Hanisch, A.; Schmalz, H.; Muller, A. H. E. J. Am. Chem. Soc. 2012, 134, 13850− 13860. (17) Bolinger, P. Y.; Stamou, D.; Vogel, H. Angew. Chem., Int. Ed. 2008, 47, 5544−5549. (18) (a) Chiu, H. C.; Lin, Y. W.; Huang, Y. F.; Chuang, C. K.; Chern, C. S. Angew. Chem., Int. Ed. 2008, 47, 1875−1878. (b) Kim, S. H.; Shum, H. C.; Kim, J. W.; Cho, J. C.; Weitz, D. A. J. Am. Chem. Soc. 2011, 133, 15165−15171. (19) (a) Stadler, B.; Chandrawati, R.; Goldie, K.; Caruso, F. Langmuir 2009, 25, 6725−6732. (b) Chandrawati, R.; Odermatt, P. D.; Chong, 363

dx.doi.org/10.1021/cm303116u | Chem. Mater. 2013, 25, 352−364

Chemistry of Materials

Article

(44) Shiomi, T.; Tsunoda, T.; Kawai, A.; Mizukami, F.; Sakaguchi, K. Chem. Mater. 2007, 19, 4486−4493. (45) Dang, F.; Enomoto, N.; Hojo, J.; Enpuku, K. Ultrason. Sonochem. 2010, 17, 193−199. (46) Rallison, J. M. Annu. Rev. Fluid Mech. 1984, 16, 45−66. (47) (a) Morais, J. M.; Rocha, P. A.; Burgess, D. J. Langmuir 2009, 25, 7954−7961. (b) Morais, J. M.; Santos, O. D. H.; Friberg, S. E. J. Dispers. Sci. Technol. 2010, 31, 1019−1026. (48) (a) Tang, X. H.; Liu, S. W.; Wang, Y. Q.; Huang, W. P.; Sominski, E.; Palchik, O.; Koltypin, Y.; Gedanken, A. Chem. Commun. 2000, 2119−2120. (b) Palani, A.; Wu, H. Y.; Ting, C. C.; Vetrivel, S.; Shanmugapriya, K.; Chiang, A. S. T.; Kao, H. M. Microporous Mesoporous Mater. 2010, 131, 385−392. (49) (a) Vincent, R. R. R.; Gillies, G.; Stradner, A. Soft Matter 2011, 7, 2697−2704. (b) Wooster, T. J.; Golding, M.; Sanguansri, P. Langmuir 2008, 24, 12758−12765. (c) Mezzenga, R.; Folmer, B. M.; Hughes, E. Langmuir 2004, 20, 3574−3582. (50) Kabal’nov, A. S.; Pertzov, A. V.; Shchukin, E. D. Colloids Surf. 1987, 24, 19−32. (51) Fryd, M. M.; Mason, T. G. J. Phys. Chem. Lett. 2010, 1, 3349− 3353. (52) Liu, J.; Yang, Q. H.; Zhang, L.; Yang, H. Q.; Gao, J. S.; Li, C. Chem. Mater. 2008, 20, 4268−4275. (53) Lin, Y. S.; Hurley, K. R.; Haynes, C. L. J. Phys. Chem. Lett. 2012, 3, 364−374. (54) Kabalnov, A.; Wennerstrom, H. Langmuir 1996, 12, 276−292. (55) Hong, L. Z.; Sun, G. Q.; Cai, J. G.; Ngai, T. Langmuir 2012, 28, 2332−2336. (56) Schmidts, T.; Dobler, D.; Guldan, A. C.; Paulus, N.; Runkel, F. Colloids Surf., A 2010, 372, 48−54. (57) (a) Chavez-Paez, M.; Quezada, C. M.; Ibarra-Bracamontes, L.; Gonzalez-Ochoa, H. O.; Arauz-Lara, J. L. Langmuir 2012, 28, 5934− 5939. (b) Rojas, E. C.; Staton, J. A.; John, V. T.; Papadopoulos, K. D. Langmuir 2008, 24, 7154−7160. (58) Kao, K.-C.; Tsou, C.-J.; Mou, C.-Y. Chem. Commun. 2012, 48, 3454−3456. (59) (a) Kamat, N. P.; Katz, J. S.; Hammer, D. A. J. Phys. Chem. Lett. 2011, 2, 1612−1623. (b) Meeuwissen, S. A.; Kim, K. T.; Chen, Y.; Pochan, D. J.; van Hest, J. C. M. Angew. Chem., Int. Ed. 2011, 50, 7070−7073. (60) (a) Mitragotri, S.; Lahann, J. Nat. Mater. 2009, 8, 15−23. (b) Du, L.; Liao, S. J.; Khatib, H. A.; Stoddart, J. F.; Zink, J. I. J. Am. Chem. Soc. 2009, 131, 15136−15142. (61) Zhang, T.; Ge, J.; Hu, Y.; Zhang, Q.; Aloni, S.; Yin, Y. Angew. Chem., Int. Ed. 2008, 47, 5806−5811. (62) Zhang, Y.; Faraone, A.; Kamitakahara, W. A.; Liu, K.-H.; Mou, C.-Y.; Leao, J. B.; Chang, S.; Chen, S.-H. Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 12206−12211.

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