pH-Triggered Drug Release Controlled by Poly(Styrene Sulfonate) Growth Hollow Mesoporous Silica Nanoparticles.

In the current report, hollow mesoporous silica (HMS) nanoparticles were successfully prepared by means of a hard-templating method and further modified with poly(styrene sulfonate) (PSS) via radical polymerization. Structural analysis, surface spectroscopy, and thermogravimetric characterization confirmed a successful surface modification of HMS nanoparticles. A hairy PSS was clearly visualized by high-resolution transmission electron microscopy measurement, and it is grown on the surface of HMS nanoparticles. The Brunauer-Emmett-Teller surface area and average pore size of HMS nanoparticles were reduced after surface modification because of the pore-blocking effect, which indicated that the PSS lies on the surface of nanoparticles. Nevertheless, the PSS acts as a "nano-gate" to control the release of curcumin which is triggered by pH. The drug-release profile of unmodified HMS nanoparticles showed a stormed release in both pH 7.4 and 5.0 of phosphate buffer saline buffer solution. However, a slow release (9.92% of cumulative release) of curcumin was observed at pH 7.4 when the surface of HMS nanoparticles was modified by PSS. The kinetic release study showed that the curcumin release mechanism from PSS@HMS nanoparticles followed the Ritger-Peppas kinetic model, which is the non-Fickian diffusion. Therefore, the PSS-decorated HMS nanoparticles demonstrate potential for pH-triggered drug release transport.

Introduction

Methods have been established to fight cancer, including surgery, radiotherapy, and chemotherapy.[1,2] Despite their advantages in promoting apoptosis of almost all cancer cell lines, the chemoagents (alkylating agents and antimetabolites) are also cytotoxic to normal cells, damage the DNA and even the immune system, and change the normal building blocks of RNA and DNA.[3,4] Moreover, there are at least 40 side-effects experienced by patients caused by cytotoxic chemoagents, such as anaphylaxis, cytopenias, hepatotoxicity, cardiotoxicity, diarrhea, nausea or vomiting, and many more.[5,6] Reduction in the dose of chemoagents not only restricts their effectiveness toward cancer cells but also leads to inadequate treatment and a slow recovery period.[7] Compared to the chemoagents, the biologically active compounds of the medicinal plants possess potent anti-inflammatory, antibacterial, antioxidant, and anticancer activity, which cure various diseases such as cancer without causing toxicity.[8] One of the safe, inexpensive, and readily available natural compounds that have been used for an anticancer drug is curcumin.[9,10]

Curcumin (diferuloylmethane) is a naturally occurring compound extracted from Curcuma longa plant which possesses anticancer activity and has a variety of therapeutic properties including antioxidant, anti-inflammatory, analgesic, and antiseptic activities.[11−13] Unfortunately, curcumin lacks water solubility and bioavailability.[14,15] Therefore, the development of a drug delivery system to deliver curcumin is mandatory in order to improve solubility and bioavailability of curcumin, thereby increasing its therapeutic activities. Nasrallah et al. successfully improved the in vitro release performance of curcumin (as shown by improving the Higuchi dissolution constant) in simulated physiological conditions by doping the curcumin to ZnO nanoparticles.[16] Encapsulation of curcumin by poly(l-lysin)-silica sol microcapsules was enabled the production of a strong free radical scavenging activity, which indicated the applicability of this system for poorly water-soluble drug models.[17] In addition to these examples, various drug carriers, such as organic polymer-based [poly(lactic-co-glycolic acid),[18] starch,[19] lipid nanocapsules,[20] microbubbles,[14] gelatin/sodium alginate,[21] chitosan,[22] etc.], inorganic-based (silica nanoparticles,[23−25] magnetite nanoparticles,[26] etc.), and hybrid organic–inorganic (vanillin–chitosan-coated calcium ferrite,[27] polymer-coated magnetite nanoparticles,[28,29] cellulose–halloysite nanotube hydrogel,[30] polymer-coated mesoporous silica,[31−33] etc.), have been reported to be capable of improving activity of curcumin. Among them, mesoporous silica nanoparticles (MSNs) are a promising candidate for a drug delivery carrier because they have a high surface area and pore volume, tunable pore diameter, are rich in hydroxyl groups for functionalization, and are biocompatible.[34] The current issues in the development of MSNs as drug carriers are the improvement of drug storage capacity and design of controlled- and targeted-drug release. In order to improve the drug storage capacity of MSNs, various shapes of MSN nanostructures are developed, such as spherical shape,[23,25,31−33] nanocubes,[24] rodlike nanostructures,[35−37] hollow nanostructures,[38−40] and so forth. The current finding demonstrates that the hollow nanostructure of MSNs has high drug storage capacity because of the presence of a hollow interior devoted to entrap a large quantity of drugs.

Hollow mesoporous silica (HMS) nanoparticles are one of MSNs platform member, having a superior pore volume to provide more room for guest molecule storage.[38,40] Compared to the solid MSNs, the HMS nanoparticle reveals unique advantages in mass diffusion and transportation because of the presence of cavities and mesoporous shells.[41] Although the HMS nanoparticle provides a large cavity to accommodate more guest molecules, it still lacks drug release ability as a result of weak interaction between unmodified nanoparticles with entrapped drug molecules which limit its capability to carry drugs to the targeted cells.[42] Modification of MSNs with polymers was reported as one such approach to protect the entrapped guest molecules effectively from premature release and degradation before reaching the targeted cells.[43] The polymer acts as a barrier for drug release on the physiological environment (pH = 7.4) but storm release is achieved at either cancer cells (pH = 5.5–4.5) or their microenvironment (pH = 6.9–6.5).[44]

Polymers like polyelectrolytes are capable of acting as a “nano-gate” to control the drug release that is triggered by pH. Generally, the polyelectrolyte-coated drug carrier-based silica nanoparticles are composed of an assembled multilayer of positively charged poly(allylamine hydrochloride) (PAH) and negatively charged poly(styrene sulfonate) (PSS) as reported by previous studies.[45−47] In some reports, a single polyelectrolyte, a positively charged PAH, was employed to develop pH-triggered drug carrier-based polymeric nanocapsules.[48,49] A slow-release mechanism of curcumin which followed the Higuchi kinetic release mechanism was observed from the PAH-based nanocapsules, in which the maximum release of curcumin was found in basic media rather than in acidic and neutral media. Because of the targeted-release of drugs in the cancer environment (the pH more acidic than normal cells),[44] a negatively charged polyelectrolyte like PSS was employed in our study. In this study, the HMS nanoparticles were surface-modified by growing a negatively charged polyelectrolyte PSS as a nanogate in order to control the curcumin drug release and to give a negative surface charge under a neutral condition. This is important to prevent the electrostatic interaction between nanoparticles with negatively charged plasma or blood cells, which caused toxicity during drug transport.[50] In addition, surface engineering of particles by grafting PSS could improve the in vitro and in vivo osteoblast cell response, and enhance the cell adhesion and differentiation because of the presence of SO3– groups.[51] Recently, surface modification of silica nanoparticles by polyelectrolytes was achieved by physical modification, such as layer-by-layer and physical adsorption that have weak interaction to the surface of nanoparticles. Alternatively, radical polymerization of PSS is one of the chemical modification methods to attach the polymer tightly on the surface of nanoparticles. To the best of our knowledge, the growth of polyelectrolyte especially PSS via radical polymerization on the surface of HMS nanoparticles is not yet studied and reported. A combination of high storage capacity of the HMS and the nanogate features of PSS will create a powerful drug delivery carrier. Herein, we construct HMS nanoparticles and further chemically modify them with PSS as pH-triggered drug delivery carriers.

Results and Discussion

Synthesis of HMS and PSS@HMS

The PSS@HMS nanoparticles were prepared through three steps of reaction as shown in Figure , that is, preparation of HMS nanoparticles, silylation of HMS nanoparticles, and polymerization of styrene sulfonate monomers on silylated-HMS surfaces. The presence of vinyl groups on the surface of HMS nanoparticles provided active sites for polymerization of styrene sulfonate which promoted by the radical reaction. AIBN is a powerful radical initiator for promoting a radical polymerization under mild temperature conditions. The polymerization was terminated by adding cold methanol into the suspension. In the last steps, the sodium ion was ionic-exchanged to form PSS.

Figure 1

Synthesis illustration of PSS@HMS nanoparticles.

Both HMS and PSS@HMS nanoparticles were characterized by Fourier transform infrared (FTIR) spectroscopy for functional group analysis. The FTIR spectra of HMS as depicted in Figure a shows typical peaks of Si–O and O–H stretching vibration at around 1100 and 3400 cm–1, respectively. Peaks at around 1700 and 1400 cm–1 are characteristic of C=O and C=C stretching vibration, respectively. Decorating PSS onto HMS surfaces can be proven by the presence of asymmetric and symmetric vibration of S=O groups at around 1170 and 1040 cm–1, respectively. This data confirms that the presence of a new functional group associated with PSS functional groups is found on the PSS@HMS sample. Therefore, it can be assumed that the PSS was successfully grown on the HMS surfaces.

Figure 2

(a) ATR–FTIR spectra and (b) low-angle XRD patterns of HMS and PSS@HMS.

The structure of HMS and PSS@HMS nanoparticles were compared by low-angle X-ray diffraction (XRD) analyses. Figure b reveals the low angle XRD patterns of HMS and PSS@HMS, which confirms that both HMS and PSS@HMS nanoparticles have similar patterns to MCM-41. At a glance, the PSS@HMS XRD pattern appears almost identical to that of unmodified HMS nanoparticles. It implies the mesostructure of HMS preserved after modification. However, there is a shift of 2θ at ca. 2.1–2.3° after modification (silylation and growing PSS on the HMS surfaces). The d100-basal spacing of HMS is found to be 42.05 Å. Functionalization and introduction of PSS on the HMS surfaces decrease the d100-basal spacing to 38.83 Å. It can be attributed to the formation of a siloxane network of TMPMA between the (100) planes of HMS. The shift and decrease in intensity of the XRD peak for PSS@HMS nanoparticles signify that modification occurs not only in the surface of HMS nanoparticles but also inside their pore channels which affects the size of the average pore diameter.[52]

Figure shows X-ray photoelectron spectroscopy (XPS) spectra of HMS and PSS@HMS. The peaks appearing at a binding energy of 532.5, 154.5, and 103.5 eV are attributed to the O 1s, Si 1s, and Si 2p electrons, respectively, detected at both HMS and PSS@HMS XPS spectra. New peaks were observed on the PSS@HMS XPS spectra at a binding energy of 284.5 and 167.5 eV associated with C 1s and S 2p, respectively, confirming the presence of PSS in the HMS surfaces. Accordingly, the Si 2p core-level XPS spectra of PSS@HMS as shown in Figure b reveals three chemical bonding states, Si–O, Si–O–C, and Si–C located at each binding energy of 102.1, 102.7, and 103.27 eV, that appeared on PSS@HMS surfaces.[53,54] A deconvolution of C 1s core-level XPS spectra (Figure c) shows characteristic signals of C=O (sp2 288.1 eV), which correspond to the carbonyl group of TMPMA. The other two signals are C–C (sp3 285.1 eV) and C=C (sp2 283.9 eV), assigned for a backbone chain and benzene ring of PSS.[55,56] In addition, a weak signal at 167.5 eV, which is only found at PSS@HMS XPS spectra, is a characteristic peak of S 2p of −SO3Na, the side groups of PSS. The deconvolution S 2p core-level XPS spectra (Figure d) indicates two signals at a binding energy of 167.3 eV (S 2p3/2) and 168.5 (S 2p1/2) assigned for the −SO3Na characteristic peak.[57] The presence of these peaks designated that the PSS successfully anchored to the HMS surfaces. It is also supported by elemental analysis (Table S1) generated from XPS spectra, showing that the S atom is only found in PSS@HMS by 2.17%.

Figure 3

(a) XPS spectra of HMS and PSS@HMS nanoparticles. (b) Si 2p, (c) C 1s, and (d) S 2p core-level XPS spectra of PSS@HMS nanoparticles.

Previously, the structural and surface characterization confirmed that the PSS was successfully grown on the surface of HMS nanoparticles. In order to support these data, a thermal gravimetric analysis (TGA) characterization was performed as one of the powerful tools for semiquantitative analysis, analyzing the presence of PSS on the surface of HMS nanoparticles. As shown in Figure , HMS nanoparticles demonstrate one consecutive weight loss meanwhile PSS@HMS nanoparticles have three. The HMS nanoparticles exhibit a weight loss of about 18% in the temperature range 30–100 °C with an endothermic reaction, indicating a loss of water molecules. A monotonical decrease is found and it reaches a plateau at above 300 °C, corresponding to removal of water molecules entrapped inside the pore structure and hollow interior. A loss of water molecules is also observed in the PSS@HMS nanoparticle TGA curve of about 11% and undergoes an insignificant decrease until a temperature of around 300 °C. A second stage degradation of about 8% occurs in the temperature range 300–480 °C, which is a contribution from desulfonation and destruction of the PSS backbone.[58] The third step is an exothermic reaction of the silane compound and side-chain degradation occurred in the temperature range 504–544 °C.

Figure 4

TG and DSC profiles of HMS and PSS@HMS nanoparticles.

Morphology and Textural Properties

Field-emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HRTEM) analysis are intensely used to study the morphology of materials, and they are powerful tools to help in visualizing the structure of nanoparticles.[59] An FESEM image of HMS nanoparticles (Figure a) shows well-shaped spherical nanoparticles with an average particle size of 81.45 ± 17.21 nm. A hollow interior of HMS nanoparticles is clearly visible in the center and edge of the nanoparticles as depicted in the inset image of Figure a. In addition, the HMS nanoparticles have uniform particle size distribution as shown in Figure b. Silylation and further polymerization of PSS on the surface of HMS nanoparticles do not gradually change their morphology. However, the nanoparticles appear to stick together as observed in Figure c. The hairy PSS is noticeably observed by HRTEM measurement (Figure d) on the surface of HMS.

Figure 5

(a) FESEM image (insert image indicates HRTEM of HMS nanoparticles, scale bar = 20 nm) and (b) particle size distribution of HMS nanoparticles. (c) SEM image and (d) HRTEM image of PSS@HMS nanoparticles.

The previous result has described the structural and morphological characteristics of HMS and PSS@HMS nanoparticles. However, in order to confirm the mesoporous properties of both nanoparticles, it is important to perform the N2 adsorption–desorption characterization. The result (Figure ) reveals a type IV of the N2 adsorption–desorption isotherm for both HMS and PSS@HMS nanoparticles, indicating a characteristic of mesoporous materials with capillary pore geometry. The distinction between these two nitrogen adsorption–desorption isotherms lies in their hysteresis loop because of the presence of PSS on the surface of HMS nanoparticles. It also affects the Brunauer–Emmett–Teller (BET) surface area and the average pore diameter of HMS nanoparticles. HMS nanoparticles have a high BET surface area of 1116.66 m2 g–1 with a regular pore diameter of 18.86 Å. Functionalization and growing PSS in the surface of HMS nanoparticles gradually decrease the BET surface area to 519.53 m2 g–1. The polymer backbone of PSS may completely cover the surface of HMS nanoparticles as observed in the nitrogen adsorption–desorption isotherm which was also supported by TEM measurement. Consequently, the average pore diameter of PSS@HMS nanoparticles decreases to 16.84 Å. The same results were also found by previous research after modifying, grafting, or decorating the surface of nanoparticles either by polymer, silane compounds, or organic moieties.[23,60]

Figure 6

N2 adsorption–desorption isotherms of HMS and PSS@HMS. The inset images indicate the pore size distribution of each nanoparticle.

Figure shows the hydrodynamic particle size of PSS@HMS nanoparticles measured under various pH conditions of phosphate buffer saline (PBS) solution (pH = 3–7). The data clarifies that the nanostructure size of PSS@HMS dynamically changes as a consequence of the pH values. The average hydrodynamic particle size of PSS@HMS was found to be 344.2 nm (PDI = 0.398) at pH 7, but increased to be 425.5 nm (pH 6, PDI = 0.434), 405.6 nm (pH 5, PDI = 0.383), 546.1 nm (pH 4, PDI = 0.495), and 438.9 nm (pH 3, PDI = 0.420). The increasing hydrodynamic particle size of PSS@HMS nanoparticles is because of the structural conformation of the hairy PSS polymer which is affected by pH of the environment. As revealed in TEM measurements, the hairy PSS polymers are found to stick to the surface of the nanoparticles. By increasing the pH, the polymer backbone expands in all directions (as illustrated in the inset image in Figure ) because of electrostatic repulsion of the positively charged polymer. Consequently, the hydrodynamic particle size of PSS@HMS nanoparticles increases under acidic conditions.

Figure 7

Hydrodynamic particle size of PSS@HMS nanoparticles measured by the DLS method at various buffered-pH solutions.

As shown in Figure S3, the zeta (ζ)-potential of PSS@HMS nanoparticles is −29.00 ± 0.75 mV (PDI = 0.398) at pH 7 of PBS solution. It indicates a moderately stable suspension which reflects a good dispersibility. Because the nanoparticles have relatively high ζ-potential as a function of pH, the PSS@HMS nanoparticles are difficult to agglomerate which directly minimize their toxicity.[61,62] The ζ-potential, also known as electro kinetic potential, not only reflects the suspension stability of materials but also indicates the surface charge of nanoparticles.[63] The surface charge of PSS@HMS nanoparticles at pH 7 of PBS solution is negative, thereby minimizing the electrostatic interaction with the negative charge of plasma or blood cells. The pH value of PBS solution influenced the surface charge of PSS@HMS nanoparticles. The ζ-potential of nanoparticles becomes more positive in acidic solution because of the protonation of PSS. This positive charge makes nanoparticles easily penetrate the cancer cells (acidic environment).

In Vitro Release Study of Curcumin

To investigate the pH-dependent drug release of HMS and PSS@HMS, the in vitro drug release experiment was carried out at two different pH values, that is, pH = 7.4 and 5.0 as representative of physiological and cancer environment conditions.[43,44] The drug release study was monitored for both unmodified HMS and PSS@HMS nanoparticles. There is no initial burst release of curcumin observed in both nanoparticles as shown in Figure . The cumulative release of curcumin from all of nanoparticles is less than 50% even when the experiment was carried out until 43 h. The drug release profiles of curcumin-loaded HMS (HMS-Cur) nanoparticles at the two different pH values show an insignificant difference. It indicates that the HMS without modification is unable to control the drug release which triggered by pH. On the contrary, a very slow curcumin drug-release profile (9.92%, ca. = 1.79 mg L–1) is achieved at pH 5.0, while a storm release (22.27%, ca. = 4.03 mg L–1) is clearly observed at pH 7.4 for PSS@HMS nanoparticles. This finding proves that the polyelectrolyte PSS acts as a barrier to prevent premature release of drugs from the drug carrier, the so-called “nano-gate”.[45,46]

Figure 8

In vitro release profile of HMS-Cur and PSS@HMS-Cur at pH 7.4 and 5.0.

The mechanism of drug release of curcumin from PSS@HMS nanoparticles can be explained based on the structural behavior of PSS toward the pH. It was previously described from dynamic light scattering (DLS) analysis that by decreasing pH (acid condition), the polymer backbone of PSS expanded due to a high positive charge (ζ-potential = +35.66, Figure S3). It enables the curcumin molecules to easily escape from the PSS@HMS nanoparticles. Moreover, the hydrogen bonding between PSS and curcumin is disturbed at low pH, in which the sulfonate group is protonated. A similar mechanism was also proposed by Nasab et al., in which they prepared chitosan-capped MSNs as pH-responsive drug carriers.[31] At low pH, the ionizable functional groups of the polymer are protonated, creating a cationic polyelectrolyte. Consequently, the polymer is swelled because of its repulsive force between the positively charged chains. In this state, the number of released curcumin increases.

Kinetic Study of Curcumin Release

The study of kinetic drug release is critically important to understand the drug-release mechanism along with better prediction of the in vitro and even in vivo temporal drug release from host materials. Ritger–Peppas and Higuchi kinetic release models were considered to mathematically study the release mechanism and kinetic release rate of curcumin from HMS and PSS@HMS nanoparticles.[64−66] Nonlinear fitting data to the models is shown in Figure S4 and the parameters’ values are presented in Table . According to the Ritger–Peppas model, the drug-release mechanism for a spherical sample is divided into three categories based on the diffusion exponent (n) value, that is, n ≤ 0.43 (Fickian diffusion), 0.43 < n < 1 (anomalous (non-Fickian) transport), and n = 1 (zero-order release). All of the nanoparticles reveal the diffusion exponent (n) value between 0.43 and 1 which indicates the non-Fickian drug-release mechanism, except for the curcumin released from HMS at pH 7.4 of PBS solution which follows the Fickian release mechanism. The data shows that the release mechanism of curcumin from HMS nanoparticles strongly depends on the pH of the environment as a driving force for curcumin diffusion from the HMS nanostructure to the PBS solution. Meanwhile, the curcumin release mechanism of PSS@HMS nanoparticles is influenced not only by the media environment but also by the structural behavior of the PSS polymer chain at different pH values. It was previously discussed that the polymer chain of PSS expanded in an acidic medium and shrank at neutral pH (illustrated in Figure ). This phenomenon supports the kinetic release mechanism of PSS@HMS which follows the non-Fickian release mechanism according to the Ritger–Peppas model. In order to confirm the Fickian release mechanism of HMS at pH 7.4, the Higuchi kinetic model is studied. The Higuchi model fits to demonstrate the Fickian release mechanism and is frequently applied to describe the drug-release mechanism from the thin-film ointment.[67,68] Nevertheless, this model also can be used for spherical systems as reported by previous research.[16,17,48,49] As expected, the correlation coefficient (R2) of the Higuchi model for curcumin release from HMS nanoparticles at pH = 7.4 is higher than that of other systems. This strongly confirms that the curcumin release mechanism of HMS nanoparticles (pH = 7.4) follows Fickian diffusion (obeys the Fick’s law).

Table 1

Release Kinetic Parameters Obtained from Nonlinear Fitting Plots of Ritger–Peppas and Higuchi Models

		Ritger–Peppas			Higuchi
material	pH	k (h–1)	n	R2	kH (% h–1)	R2
HMS	5.0	0.1766	0.7279	0.9755	6.5209	0.9182
	7.4	0.3114	0.4147	0.9559	5.3706	0.9402
PSS@HMS	5.0	0.1106	0.9503	0.9895	5.6515	0.8446
	7.4	0.1649	0.8029	0.9817	2.8426	0.8916

Table also shows the Ritger–Peppas kinetic release rate (k) and Higuchi dissolution (kH) constants. The k value of PSS@HMS nanoparticles is lower than unmodified-HMS nanoparticles at both pH 5.0 and 7.4 which indicates a slow release rate of curcumin. The k value depends on the structural and geometrical characteristics of particles.[68] Therefore, the release rate of curcumin from PSS@HMS nanoparticles slows down because of the presence of PSS on the surface of nanoparticles which extend the diffusion rate of curcumin from one site to another site until it releases to the PBS medium. In this study, the Higuchi dissolution constant (kH) is also measured. It can be found that the kH of PSS@HMS at pH 5.0 is 5.6515% h–1 two times higher than that at pH 5.0. The kH value depends on the particle size, where it increases with the increase in the hydrodynamic particle size.[48] As shown in Figure , the hydrodynamic particle size of PSS@HMS at pH 5.0 is higher than that of PSS@HMS nanoparticles measured at pH 7.0.

Conclusions

In summary, HMS nanoparticles, fabricated by hard-templating methods, were successfully decorated by PSS via radical polymerization which was confirmed by structural analysis, surface spectroscopy, and thermogravimetric and morphological studies. The presence of PSS on the surface of HMS can be visualized by HRTEM measurements like a hair sticking on the surface of HMS nanoparticles. Modification of HMS nanoparticles by growing PSS on their surface affects their textural properties by decreasing the BET surface area and reducing the average pore size. Nevertheless, the BET surface area of PSS@HMS nanoparticles is still higher, fulfilling the requirement as a drug carrier. It is proved by a high loading capacity of up to 85.48%. The presence of PSS as a nanogate on the surface of HMS nanoparticles enables them to control the drug release of curcumin triggered by pH, which cannot be achieved by unmodified-HMS nanoparticles. The in vitro drug release study of curcumin from PSS@HMS nanoparticles revealed that a slow release of curcumin was found under physiological conditions, but it was stormed out under acidic conditions. The kinetic release study demonstrated that the Ritger–Peppas drug release model played a role in determining the release mechanism of curcumin from nanoparticles, in which the release of curcumin from PSS@HMS was followed by non-Fickian diffusion in both pH 7.4 and 5.0.

Experimental Section

Synthesis of HMS Nanoparticles

HMS nanoparticles were prepared by the hard-templating method. The as-prepared solid template, l-serine-capped magnetite nanoparticles (l-ser@MNP procedure available in Supporting Information), was added into stabilized surfactant micelle solution, which was prepared by adding 0.125 g hexadecyl trimethylammonium bromide into a mixture solution of ethanol (3 mL) and distilled water (60 mL) at 80 °C for 1 h, pH = 10 adjusted by NH4OH. The mixture was stirred for 1 h at 800 rpm. Afterward, 50 μL of TEOS was wisely added to the suspension and stirred for 20 h. The intermediate product was collected by centrifugation, washed with distilled water, and redispersed in methanol for template removal. To the suspension, 2 mL of HCl was added and stirred overnight (this procedure was repeated twice). Then, the HMS nanoparticles were collected by centrifugation, washed several times with distilled water, and dried by a freeze-drying machine. The HMS nanoparticles were structurally characterized by attenuated total reflectance FTIR (ATR–FTIR, PerkinElmer Spectrum 400), low angle powder XRD (Rigaku MiniFlex600), XPS (Quantera SXM-GS), and TGA (STA Lineises PT-1600). The morphology of the nanoparticles was observed by FESEM (Hitachi S-4800) and HRTEM (JEOL JEM-2100). The N2 adsorption–desorption isotherm was measured to determine the BET surface area and pore size of the nanoparticles.

Synthesis of PSS-Decorated HMS Nanoparticles

Two step reactions were involved in the synthesis of PSS-anchored HMS nanoparticles, namely, silylation and polymerization. About 0.1 g of HMS nanoparticles were dispersed in 50 mL of toluene and stirred under a nitrogen atmosphere. Then, 48 μL (0.2 mmol) of 3-(trimethoxysilyl) propyl methacrylate (TMPMA, Sigma-Aldrich) was added to the suspension and refluxed for 24 h. The silylated HMS was collected by centrifugation and washed with fresh toluene, ethanol, and distilled water, sequentially. Then, it was redispersed in 5 mL of distilled water. Afterward, 70 μL of N,N′-azobisisobutyronitrile (AIBN, 15% in acetone, Sigma-Aldrich) was dropped and mildly stirred at 70 °C for 10 min. About 0.2072 g (1 mmol) of sodium-4-vinyl benzene sulfonate (Na-VBS, Sigma-Aldrich) was dissolved in 5 mL distilled water and directly added into the suspension. Polymerization was terminated by adding cold methanol after 20 h of reaction. The product was soaked in 50 mL of 0.1 M HCl overnight and collected by centrifugation. The PSS-decorated HMS nanoparticles (denoted as PSS@HMS) were repeatedly washed with distilled water and dried using a freeze-drying machine. Then, the PSS@HMS nanoparticles were characterized by using techniques such as FTIR, low-angle XRD, XPS, TG/DSC, FESEM, HRTEM, N2 adsorption–desorption. The hydrodynamic particle size and zeta potential of the PSS@HMS nanoparticles were evaluated by a Zetasizer (Malvern).

Study of in Vitro Release of Curcumin

Adsorption of curcumin was performed under room temperature. About 0.1 g of nanoparticles was added into 20 mL of curcumin solution (200 mg L–1 in ethanol/water 3:7) and stirred for 24 h. Afterward, the nanoparticles were collected by centrifugation and the remaining solution was measured using UV–vis spectrophotometry (U-4100 Hitachi) to determine the loaded amount of curcumin. The adsorption efficiency of HMS and PSS@HMS nanoparticles toward curcumin was found to be 83.52 and 85.48% (Table S2).

The release of curcumin from nanoparticles carried out under two conditions, PBS solution pH = 7.4 and pH = 5.0. About 10 mg of curcumin-loaded nanoparticles were soaked in PBS solution and shaken at 200 rpm. The supernatant (10 mL) was collected and measured by UV–vis spectroscopy (U-4100 Hitachi) to determine the release amount of curcumin. The cumulative release of curcumin from either HMS or PSS@HMS was defined as the amount of curcumin released into solution per amount of curcumin adsorbed onto nanoparticles.