Yolk–Shell Structured Mesoporous Nanoparticles with Thioether

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Yolk−Shell Structured Mesoporous Nanoparticles with ThioetherBridged Organosilica Frameworks Zhaogang Teng,†,Δ Xiaodan Su,‡,Δ Binghui Lee,§ Chungui Huang,§ Ying Liu,† Shouju Wang,† Jiang Wu,† Peng Xu,¶ Jia Sun,¶ Dengke Shen,⊥ Wei Li,⊥ and Guangming Lu*,† †

Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002 Jiangsu, P.R. China Key Laboratory for Organic Electronics & Information Displays and Institute of Advanced Materials, Nanjing University of Posts and Telecommunications, Nanjing, 210046 Jiangsu, P.R. China § Materials Science Laboratory, SAE Magnetics (H.K.) Ltd., Nancheng, Dongguan City, 523087 Guangdong, P.R. China ¶ College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037 Jiangsu, P.R. China ⊥ Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Laboratory of Advanced Materials, Fudan University, Shanghai 200433, P.R. China ‡

S Supporting Information *

ABSTRACT: Organic functionalization and structural control of mesoporous materials are important for their applications. This study reports here that yolk−shell structured mesoporous nanoparticles with thioether-bridged organosilica frameworks can be successfully prepared by hydrothermal treatment of mesostructured organic−inorganic hybrid nanospheres. The thioether-bridged yolk−shell nanoparticles have ultrahigh condensation degree, i.e., (T3+Q4)/(Qn+Tm) = 94%, large surface area (400 m2 g−1), accessible ordered mesochannels (2.0 nm), large pore volume (0.67 cm3 g−1), and uniform diameter (290−90 nm), core size (180−40 nm), and shell thickness (19−8 nm). Thanks to the abundant thioether groups and the unique structure, the yolk−shell mesoporous nanoparticles can be used as nanoreactors to generate in situ polyhedral gold nanoparticles into their hollow spaces in a hot tetrachloride aurate aqueous solution. The gold loaded yolk−shell nanoparticles show two strong plasmon resonance bands at 577 and 633 nm with excellent photothermal efficiency. This shows a great potential for photothermal treatment. Furthermore, the thioether-bridged yolk−shell mesoporous nanoparticles exhibited excellent capability for convenient covalent connection of near-infrared dyes, which make them promising candidates for applications in cell and tumor imaging.

1. INTRODUCTION Ordered mesoporous silica1−4 obtained by surfactant-templated synthesis has attracted widespread interest because of their potential applications in separation,5,6 catalysis,7 and drug delivery.8 Organic functionalization and morphology control of mesoporous silica materials are important for their property profiles and practical applications.9−12 The organically functionalized mesoporous siliceous materials are usually obtained through postgrafting or a cocondensation method by using terminal trialkoxyorganosilanes of the type (R′O)3SiR.11,13−15 However, the mesochannels are narrowed or even blocked by postgrafting of the trialkoxyorganosilanes, and the modified groups on the pore surfaces are often inhomogeneous.16−18 On the other hand, cocondensation of the organic silanes in the mesoporous silica frameworks generally induces the decreasing of their pore ordering.13,18,19 The discovery of periodic mesoporous organosilicas (PMOs) synthesized by using bridged silsesquioxane as precursors opened up a new avenue for organic group functionalized mesoporous siliceous materials.20−24 Unlike the organically functionalized mesoporous silica © XXXX American Chemical Society

prepared by grafting or cocondensation of trialkoxyorganosilanes, the mesopores are not blocked, and ordered mesostructures can be well retained even the bridged silsesquioxane in mesoporous frameworks is up to 100%.25,26 As ideal organic functionalized mesoporous materials, different morphologies of PMOs, such as particles,20 rods,27 films, 2 1 , 2 8 monoliths, 2 9 and hollow or yolk−shell spheres,24,30−33 have been controllably synthesized for various practical applications. Among these, yolk−shell structures have attracted increasing attention recently owing to their high surface area, uniform pore size, large pore volume, and unique hollow compartmentation spaces for confined reactions or delivery of guest molecules.31,34−36 Yolk−shell particles with a PMO shell have been prepared by coating silica cores with a mesoporous hybrid outer shell and then partly etching the cores.24 However, the synthetic strategy is challenging, because Received: July 28, 2014 Revised: September 21, 2014

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2. EXPERIMENTAL SECTION

the coating and removal procedures are complex, timeconsuming, and uneconomic. Cocondensation of bis(trimethoxysilyl)ethane (BTME) with surfactants on the surfaces of vesicles containing core particles have also been developed to fabricate the yolk−shell structure.35 However, the vesicles often represent low stability, which results in aggregated yolk−shell particles. Furthermore, the cores used in the both methods are nonporous silica, thus only the shells of the yolk−shell structures are composed of PMO frameworks. This study demonstrated that incubating mesostructured ethane-bridged organosilica spheres within water under a temperature of 70 °C can produce monodisperse yolk−shell spheres in which both the core and the shell are made of PMO.31 The method is intrinsically simple because the core particles and coating processes are not required for preparation of the yolk−shell structures. However, it is found that the mild incubation is ineffective for formation of yolk−shell structured PMOs bridged with long-chain organic groups due to their relatively low hydrophilicity and high hydrothermal stability.26 It is reported that introducing bridged organosilicas containing long-chain functional moieties, such as chiral centers,37 metal complexes,38 photoactive species,39 or heteroelement (N, S, P, etc.) fragments,40 into mesoporous frameworks can endow the PMOs with colorful properties for chiral separation, catalysis, ligtht harvesting, drug delivery, or water treatment. 25 Particularly, the sulfide moieties contained PMOs are of interest for their capability to chelate metal ions or provide sulfonic acid and thiol groups through a post-treatment.25,41−43 Therefore, it is highly desirable to develop a facile approach for synthesis of yolk−shell structured PMOs containing long-chain functional groups. Hydrothermal chemistry has become an active research subject because of its contributions to geology, energy, and various advanced materials.44−47 A temperature higher than the boiling temperature of water and high pressure can be easily achieved for various reactions in a close system by hydrothermal technology. It is reported that the dissolution and reassembly of silicate/surfactant composites may have occurred and the ordering degree of mesoporous silicas can be effectively improved through hydrothermal treatment.48,49 Herein, this study demonstrated that yolk−shell mesoporous nanoparticles with thioether-bridged organosilica frameworks can be facilely prepared by hydrothermal treatment of mesostructured organic−inorganic hybrid nanospheres in an autoclave under a temperature of 150 °C. The method is very simple and does not require hard- or soft-templates, complex coating processes, and corrosive etching agents. The thioether-bridged yolk−shell mesoporous nanoparticles obtained possess highly uniform and controllable diameter (290−90 nm), tunable core size and shell thickness, high surface area (400 m2 g−1), accessible ordered mesochannels (2.0 nm), large pore volume (0.67 cm3 g−1), and ultrahigh condensation degree. Thanks to the unique structures and the organic framents, gold polyhedron loaded yolk−shell structures can be directly prepared by using the thioetherbridged yolk−shell mesoporous nanoparticles as in situ nanoreactors, which show excellent photothermal efficiency upon laser irradiation of 635 nm. Also, near-infrared illuminated yolk−shell mesoporous nanoparticles were successfully synthesized by breaking the S−S bonds of the thioether groups to generate thiol groups and then covalently connect with Cy5.5maleimide, which show excellent in vitro and in vivo biomedical imaging capability.

2.1. Materials. Tetraethoxysilane (TEOS), cetyltrimethylammonium bromide (CTAB), concentrated ammonia aqueous solution (25 wt %), anhydrous ethanol, dioxane, triphenylphosphine, N,Ndimethylformamide, and HAuCl4·4H2O were of analytical reagent grade and obtained from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). 1,4-Bis(triethoxysily)propane tetrasulfide (TESPTS) was bought from Sigma−Aldrich (St. Louis, MO, USA). Cy5.5-maleimide was purchased from Seebio Biotechnology Co., Ltd. (Shanghai, China). Deionized water (Millipore) with a resistivity of 18 MΩ cm was used in all experiments. Dulbecco’s Modified Eagle’s Medium (DMEM), heat-inactivated fetal bovine serum (FBS), penicillin-streptomycin solution, and dimethyl sulfoxide (DMSO) were bought from Gibco Laboratories (NY, USA). 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) was obtained from Nanjing Keygen Biotech. Co., Ltd. (Nanjing, China). The human breast cancer MCF-7 cell line was purchased from American Type Culture Collection (ATCC). 2.2. Synthesis of Yolk−Shell Structured Mesoporous Nanoparticles with Thioether-Bridged Organosilica Frameworks. Mesostructured nanospheres with thioether-bridged organosilica frameworks were first prepared via a surfactant-assembly sol−gel process in a solution containing water, ethanol, ammonia, CTAB, TEOS, and TESPTS. The typical synthetic procedure is as follows: 0.16 g of CTAB was dissolved in a mixed solution containing 1 mL of concentrated ammonia aqueous solution (1 mL, 25 wt %), 30 mL of ethanol, and 75 mL of water. Then, the solution was heated to 35 °C, and a mixture of TESPTS (0.1 mL) and TEOS (0.25 mL) was rapidly added under vigorous stirring. The molar ratio of the reaction mixture was 1.00 TEOS:0.179 TESPTS:0.393 CTAB:11.84 NH 3:3727 H 2 O:461 C 2 H 5 OH. After stirring at 35 °C for 24 h, the mesostructured organic−inorganic hybrid nanospheres were collected by centrifugation and washed three times with ethanol. Afterward, the as-made mesostructured nanospheres were dispersed in 30 mL of water and transferred to a 50 mL Teflon-lined stainless-steel autoclave. The autoclave was heated in an air flow electric oven at 150 °C for 12 h and then cooled down to room temperature. The solid product was collected by centrifugation and washed with ethanol. Then, the surfactant was extracted by stirring the product in a solution containing 120 mL of ethanol and 240 μL of concentrated HCl (37%) at 60 °C for 3 h. The solvent-extraction procedure was repeated three times to completely remove the surfactant. Finally, the product was washed with ethanol three times and dried in an oven at 70 °C. 2.3. Synthesis of Gold Loaded Yolk−Shell Mesoporous Nanoparticles. The thioether-bridged yolk−shell mesoporous nanoparticles (12 mg) were homogeneously dispersed in 64 mL of HAuCl4· 4H2O (0.024 M) aqueous solution by ultrasonication. Then the mixture was stirred at 80 °C for 80 min. Finally, the product was washed five times with water and redispersed in 10 mL of water for further use. 2.4. Synthesis of Cy5.5 Grafted Yolk−Shell Mesoporous Nanoparticles. First, the S−S bonds in the yolk−shell mesoporous nanoparticles were transformed into thiol groups according to the previously reported method.43 Typically, 0.065 g of the thioetherbridged yolk−shell mesoporous nanoparticles was dispersed in a mixture of dioxane (1.1 mL) and water (0.3 mL). Then, 0.10 g of triphenylphosphine was added to the suspension. Afterward, the mixture was heated to 40 °C, and two drops of concentrated HCl (37%) were added. After reacting at 40 °C under nitrogen for 2 h, the thiol groups contained yolk−shell mesoporous nanoparticles, were washed with ethanol for three times, and dispersed in 2 mL of ethanol. To link near-infrared dyes, the above obtained suspension (0.5 mL) and Cy5.5-maleimide (0.3 mg) were added to a mixed solution of water (3.0 mL) and N,N-dimethylformamide (0.3 mL). The resulting mixture was allowed to be shaken at room temperature for 12 h. Finally, the Cy5.5 grafted yolk−shell mesoporous nanoparticles were obtained and thoroughly washed with water. They were then redispersed into water for use. To evaluate the amount of Cy5.5maleimide conjugated to the nanoparticles, the supernatant and B

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using a Lambda 35 UV−vis spectrophotometer (PerkinElmer, Inc., Waltham, MA, USA). Thermal images were obtained by a MAGNITY f15F1 infrared camera (Wuhan VST Light & Technology Co., Ltd., China). Confocal images were captured on an Olympus FV1000 LSCM with a 60× oil immersion objective (numerical aperture = 1.40). In vivo imaging was performed using IVIS Lumina XR system (Xenogen Corporation-Caliper, Alameda, CA, USA) under the Cy5.5 filter (λex = 640 nm, λem = 705 nm).

washed solutions were collected, and the free dye content was measured by using a UV−vis spectrometer at a wavelength of 677 nm. 2.5. Cytotoxicity Assay, Cell Staining, and In Vivo Fluorescence Imaging. Human breast cancer MCF-7 cells were routinely grown in DMEM supplemented with FBS (10%, v/v) and penicillin-streptomycin solution (1%, v/v). For cytotoxicity assay, the MCF-7 cells were seeded into a 96-well cell-culture plate at a density of 1 × 104 cells/well and allowed to grow for 24 h. Then, different concentrations of yolk−shell mesoporous nanoparticles dispersed in DMEM were added to the culture, and the cells were incubated for 24 h. Five duplicates wells were set up for each concentration. Afterward, 10 μL of MTT reagent (5 mg mL−1 in culture medium) was added to culture and further incubated for 4 h. Then the culture medium was removed, and 150 μL of DMSO was added to each well for dissolving the formazan crystals. Finally, the optical density (OD) was determined at 570 nm on an automated microplate reader (BioTek Instruments, Winooski, VT, USA). The cell viability was calculated according to the following equation

3. RESULTS AND DISCUSSION Mesostructured nanospheres with thioether-bridged organosilica frameworks were first prepared via a surfactant-assembly sol−gel process by using TEOS and TESPTS as precursors and CTAB as a structure-directing agent (Figure 1a and 1b). Then,

Viability (%) = (mean OD of treatment cells /mean OD of nontreated cells) × 100 For cell staining, 0.5 mL of the MCF-7 cells was seeded into a dish with a concentration of 1 × 105 cells per mL and allowed to grow for 24 h. Then, 100 μg mL−1 Cy5.5 grafted yolk−shell mesoporous nanoparticles dispersed in DMEM was added to the culture, and the cells were incubated at 37 °C for 2 h. After washing the cells with PBS once more to remove the excess nanoparticles, cell imaging was carried out on a laser scanning confocal microscope (LSCM) under the Cy5.5 filter (λex = 635 nm, λem = 650−750 nm). To carry out in vivo fluorescence imaging, a suspension of 5 × 106 MCF-7 cells in PBS (100 μL) was subcutaneously inoculated into a BALB/c female nude mouse (5 weeks old, 19−20 g). When the tumor volume was approximately 500 to 700 mm3, 50 μL of Cy5.5 grafted yolk−shell mesoporous nanoparticles in PBS (3 mg mL−1) were intratumorally injected. After 2 h, in vivo fluorescence imaging was performed using IVIS Lumina XR system under the Cy5.5 filter (λex = 640 nm, λem = 705 nm). 2.6. Characterization. Scanning electron microscopy (SEM) images were taken on a S4800 SEM (Hitachi, Tokyo, Japan) operated at 5 kV. Transmission electron microscopy (TEM) images were obtained by using an HT7700 microscope (Hitachi, Tokyo, Japan) operated at an accelerating voltage of 100 kV. Fourier transform infrared (FT-IR) spectra were obtained on a Nicolet NEXUS870 spectrometer (Nicolet Instruments Inc. Madison, WI, USA). Solidstate 13C cross-polarization/magic-angle spinning (CP/MAS) and 29Si MAS NMR spectra were recorded at 9.47 T on a Bruker AVANCE III400 spectrometer. The 13C CP/MAS NMR spectra were recorded at a 100.62 MHz by using a 4 mm probe with a contact time of 2 ms, a recycle delay of 1 s, and a spin rate of 14 kHz. Chemical shifts for 13C NMR were referenced to methine carbon atoms of adamantane. The measurements of 29Si MAS NMR spectra were performed at 79.48 MHz by using a 7 mm MAS probe with a spin rate of 6.0 kHz and a recycle delay of 120 s. Chemical shifts for 29Si NMR were referenced to 3-(trimethylsilyl)-1-propanesulfonic acid sodium salt (DSS). Inductively coupled plasma-atomic emission spectroscopy (ICPAES) was measured by using a PerkinElmer Optima-5300DV spectrometer (Perkin- Elmer, Inc., Waltham MA, USA). X-ray power diffraction (XRD) was measured on a Bruker model D8 focus diffractometer with Cu Kα radiation (0.154 nm) operated at 40 kV and 40 mA. Nitrogen sorption isotherms were measured by using a Micromeritics Tristar 3000 analyzer (Micrometrics Instruments Corporation, Atlanta, GA, USA) at −196 °C. The samples were degassed at 150 °C for 10 h before the measurements. The Brunauer− Emmett−Teller (BET) method was utilized to calculate the specific surface area (SBET) by using the adsorption data at p/p0 = 0.05−0.15. Pore size analysis was performed by applying proper nonlocal density functional theory (NLDFT) methods from the adsorption branch of isotherm. The total pore volume (Vtotal) was estimated from the adsorbed amount at p/p0 = 0.995. UV−vis spectra were obtained by

Figure 1. (a) Schematic illustration of preparation process of the yolk−shell structured mesoporous nanoparticles with thioetherbridged organosilica frameworks. (b) TEM image of the as-made mesostructured organic−inorganic hybrid nanospheres. (c-d) TEM and (e-f) SEM images of the yolk−shell mesoporous nanoparticles with thioether-bridged organosilica frameworks prepared by hydrothermal treatment of the as-made hybrid nanospheres in autoclave under a temperature of 150 °C for 12 h.

the nanospheres were hydrothermally treated at 150 °C for 12 h to form a yolk−shell structure and were extracted by acidic ethanol to remove CTAB templates, which resulted in the thioether-bridged yolk−shell mesoporous nanoparticles. The TEM images showed that the as-made organic−inorganic hybrid nanospheres had a uniform diameter of approximately 180 nm (Figure 1b). After the hydrothermal treatment, the C

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Figure 2. (a) FT-IR spectra of (i) the yolk−shell mesoporous nanoparticles with thioether-bridged organosilica frameworks prepared by a hydrothermal treatment process at 150 °C for 12 h and (ii) pure mesoporous silica nanospheres (MSNs) synthesized by using CTAB as a structuredirecting agent and TEOS as a single silica source. (b) 13C CP/MAS and (c) 29Si MAS NMR spectra of (i) as-made organic−inorganic hybrid nanospheres and (ii) the thioether-bridged yolk−shell mesoporous nanoparticles. (d) XRD pattern and (e) nitrogen sorption isotherms of the thioether-bridged yolk−shell mesoporous nanoparticles. (f) In vitro viability of human breast cancer MCF-7 cells incubated with the yolk−shell mesoporous nanoparticles at different concentrations. The inset in (d) is the mesostructural model of the yolk−shell mesoporous nanoparticles and the inset in (e) is the pore size distribution curve.

carbon species of Si−1CH22CH23CH2−S4−3CH22CH21CH2−Si (Figure 2b, curve ii), which indicated the thioether-bridged organosilica frameworks.52 It was also observed that the peaks at 17 and 59 ppm attributed to the unhydrolyzed Si-OC2H5 groups of TESPTS and TEOS disappeared after the hydrothermal treatment (Figure 2b), which suggested the Si-OC2H5 groups were completely hydrolyzed. Moreover, no carbon signals of the CTAB surfactants were observed, indicating that the surfactants had been completely removed. The 29Si MAS NMR spectrum of the as-made hybrid nanospheres showed five signals at −59 and −67 ppm, corresponding to T2 (C− Si(OSi)2(OX), X = H or Et) and T3 (C−Si(OSi)3) species, and at −92, −101, and −110 ppm, corresponding to Q 2 (Si(OSi)2(OX)2), Q3 (Si(OSi)3(OX)), and Q4 (Si(OSi)4) species (Figure 2c, curve i).31 Obviously, the T2 and Q2 peaks disappeared after the hydrothermal treatment, and only T3, Q3, and Q4 peaks were presented in the spectrum of the thioether-bridged yolk−shell mesoporous nanoparticles (Figure 2c, curve ii), which suggested that the condensation degree of the mesoporous framework was significantly increased. Quantitative analysis showed that the (T3+Q4)/(Qn+Tm) ratio of the yolk−shell mesoporous nanoparticles was as high as 94%, which suggested an ultrahigh condensation degree. At the same time, the silicon atoms at the Q sites and at the T sites were measured to be 74% and 26%, respectively. The ICP-AES measurement showed that the dissolved silica species was about 12% after the hydrothermal treatment at 150 °C for 12 h. By considering the formation of large hollow spaces, significant increase of condensation degree, and decrease of the particle diameter after the hydrothermal treatment, it was most likely that silicate-CTAB composites were dissolved and then reassembled into the frameworks in the high temperature and pressure solutions. When the as-made mesostructured organic−

TEM images clearly reveal that every nanoparticle has a dark core encapsulated in a gray layer (Figure 1c and 1d). It is also observed that the yolk−shell mesoporous nanoparticles were not aggregated and still possessed a uniform spherical shape and smooth surface after the structural transformation. Noteworthy, the diameter of the yolk−shell mesoporous nanoparticles was decreased to 155 nm after the hydrothermal treatment. The core size and shell thicknesses of the thioetherbridged yolk−shell mesoporous nanoparticles are measured to be about 80 and 13 nm, respectively. A high-magnification TEM image shows that the thioether-bridged yolk−shell mesoporous nanoparticles possessed mesochannels both in the shell and the core (Figure 1d). A low-magnification SEM image showed that the thioether-bridged yolk−shell mesoporous nanoparticles were very uniform in both size and morphology (Figure 1e), which was consistent with the TEM observations. Simultaneously, the SEM image of a broken nanoparticle by grinding further revealed the yolk−shell structure (Figure 1f). The composition and condensation degree of the thioetherbridged yolk−shell mesoporous nanoparticles were characterized by FT-IR and NMR. The FT-IR spectrum of the yolk− shell mesoporous nanoparticles displays, i.e., characteristic C− H vibration bands at 2930, 1450, and 1410 cm −1 and a C−S absorbance band at 694 cm −1 (Figure 2a, curve i),30 which suggested that the silane TESPTS had condensed in the yolk− shell mesoporous nanoparticles. In contrast, the absorbance peaks were not present on the FT-IR spectrum of pure mesoporous silica nanospheres (MSNs) prepared according to previous methods by using TEOS as the single silica precursor50,51 (Figure 2a, curve ii). The 13C CP/MAS solidstate NMR spectrum of the yolk−shell spheres showed three signals at 12, 23, and 42 ppm assigned to the 1C, 2C, and 3C D

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Figure 3. TEM images of the yolk−shell mesoporous nanoparticles with thioether-bridged organosilica frameworks synthesized with CTAB concentrations of (a) 2.1, (b) 3.2, and (c) 6.3 mmol L−1 and at ethanol/water volume ratios of (d) 0.46, (e) 0.35, and (f) 0.32. Scale bars, 200 nm.

controlled by adjusting CTAB concentration, ethanol/water ratio, or precursor content. When the CTAB concentration was fixed at 2.1 mmol L−1, the diameter, core size, and shell thickness of the yolk−shell mesoporous nanoparticles were measured to be about 290, 140, and 19 nm, respectively (Figure 3a). As the CTAB concentration increased to 3.2 and 6.3 mmol L −1, the diameter of the thioether-bridged yolk−shell mesoporous nanoparticles decreases to 245 and 132 nm (Figure 3b-c). At the same time, their core size changes to 140 and 65 nm, and the shell thickness decreases to 19 and 11 nm. On the other hand, TEM observation showed that the diameter of the yolk−shell mesoporous nanoparticle decreased from 245 to 145 and 90 nm as the ethanol/water volume ratio decreased from 0.46 to 0.35 and 0.32 (Figure 3d-f). Simultaneously, the core size changed from 180 to 54 and 40 nm, and the shell thickness decreased from 15 to 10 and 8 nm. The decrease of the nanoparticle diameter with the increase of CTAB concentration and decrease of ethanol/water ratio was believed to be attributed to the accelerated hydrolysis of silica precursors and the more rapid coassembly of hydrolyzed silanes with CTAB surfactants, which resulted in a fast nucleation and a decrease of the nanoparticle diameter. Also, the diameter of the yolk−shell mesoporous nanoparticles was also controlled by adjusting the total silica precursor content (Figure 1c and Figure S1). However, if the precursor content was lower than 0.0875 mL, only solid structured particles were obtained after hydrothermal treatment at 150 °C for 12 h. Furthermore, it was found that the shell thickness of the thioether-bridged yolk− shell mesoporous nanoparticles can be varied from 13 to 30 nm by adjusting the TESPTS/TEOS volume ratio from 0.1/0.25 to 0.1/0.1 (Figure 1d and Figure S2). This suggested the method was highly controllable. It is known that amine-containing materials have been used as reducing agents to prepare gold nanoparticles.53,54 By considering that a sulfur atom can also provide electrons and binds with precious metal atoms via lone-pair electrons, the thioether groups should act as in situ reducing agents for preparation of gold particles from gold salt solution. The produced gold nanoparticles via the reaction of TESPTS with tetrachloride aurate at 80 °C strongly support this view (Figure

inorganic hybrid nanospheres were dispersed in water and hydrothermal treated at 150 °C, the silicate-CTAB composites on the surface were more easily attacked by water molecules and dissolved. The dissolved silicate species could further reassemble into the outer layers of the hybrid nanospheres and induce the increase of condensation degree of the outer regions. As previously reported, the ordering degree of mesoporous silicas can be effectively improved through hydrothermal treatment due to the dissolution and reassembly of silicate/surfactant composites in hydrothermal conditions.48,49 Because of closing to the outer layers, the middle parts of the mesostructured hybrid nanospheres were further dissolved and redeposited on outer shells where the hydromal stability is relatively high due to the increase of condensation degree. With the dissolution and reassembly of the middle layers, large void spaces which divide the nanospheres into the core and the shell were presented, and yolk−shell structures were eventually formed. The XRD pattern of the thioetherbridged yolk−shell mesoporous nanoparticles showed two diffraction peaks, associated with the 100 and 110 reflections of hexagonal symmetry with the space group p6mm, which suggested an ordered hexagonal mesostructure (Figure 2d). Nitrogen sorption isotherms of the yolk−shell mesoporous nanoparticles showed a type IV curve with a sharp capillary condensation step and a large hysteresis loop in the p/p0 range of 0.5−1.0 (Figure 2e). This indicated a typical mesopore architecture with narrow pore size distribution. The surface area and pore volume were calculated to be as high as 400 m2 g−1 and 0.67 cm3 g−1, respectively. The pore size distribution, calculated based on the nonlocal density functional theory, revealed the thioether-bridged yolk−shell mesoporous nanoparticles had uniform mesopores of about 2.0 nm (Figure 2e, inset). Moreover, in vitro biocompatibility evaluation demonstrated that the cell viability retained above 94% when they were incubated with the yolk−shell mesoporous nanoparticles at a concentration of as high as 800 μg mL−1 for a period of 24 h, which indicated a good biocompatibility of the materials (Figure 2f). The diameter, core size, and shell thickness of the thioetherbridged yolk−shell mesoporous nanoparticles can be facilely E

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Figure 4. TEM image of yolk−shell mesoporous nanoparticles with thioether-bridged organosilica frameworks before (a-b) and after (c) loading gold polyhedron. (d) UV−vis spectrum of gold polyhedron loaded thioether-bridged yolk−shell mesoporous nanoparticles. The inset in (d) is a photograph of the gold loaded yolk−shell mesoporous nanoparticles dispersed in aqueous solution. (e) Heating curves of pure water (blue dot line) and the gold polyhedron loaded yolk−shell nanoparticle aqueous solution with a concentration of 1 mg mL−1 (red dot line). Infrared thermal images of eppendorf vials containing (f) water and (g) the gold nanoparticle loaded nanoparticle aqueous solution.

gold polyhedron loaded nanoparticles provide a great potential for their practical applications in the biomedical field, such as drug delivery and photothermal therapy. To further illustrate the potential applications of the yolk− shell mesoporous nanoparticles with thioether-bridged organosilica frameworks, the thiol groups containing yolk−shell structured mesoporous nanoparticles were prepared through breaking the S−S bonds of the thioether groups. Then, nearinfrared illuminated yolk−shell mesoporous nanoparticles were successfully prepared by connection of Cy5.5-maleimide with the thiol groups. Fluorescence images showed the obtained nanoparticle dispersion possessed strong fluorescence (Figure S5), which suggested that Cy5.5 molecules had been successfully modified on the nanoparticles. Quantified measurements indicated that the amount of Cy5.5-maleimide conjugated to the nanoparticles was up to 15.1 mg dyes per gram of nanoparticles. It is worth mentioning that no free Cy5.5 was detected from the aqueous suspension of the Cy5.5 modified nanoparticles after one month, owing to the highly condensed mesoporous frameworks and the stable thiolmaleimide linkages. The cell imaging ability of the nearinfrared illuminated nanoparticles was further investigated. After staining with the nanoparticles, the confocal image clearly showed intense fluorescence inside the MCF-7 cells (Figure 5a). Simultaneously, the nuclear and cell morphology was not affected after incubating with the nanoparticles, which indicated their good biocompatibility (Figure 5a and 5b). The overlay image further revealed that the fluorescence was from the cytoplasm of the cells. This suggested that the near-infrared nanoparticles were able to enter into the cells (Figure 4c). To demonstrate their capability for in vivo imaging, the Cy5.5 modified yolk−shell mesoporous nanoparticles were intratumorally injected into a tumor-bearing nude mouse. Obviously, a strong fluorescence signal was observed in the tumor region, and no autofluorescence was observed elsewhere

S3). Thus, we exploit the use of the prepared thioether-bridged yolk−shell mesoporous nanoparticles as nanoreactors to generate gold nanoparticles into their hollow spaces by heating them in a tetrachloride aurate aqueous solution. Uniform yolk− shell mesoporous nanoparticles with accessible ordered mesochannels were used as the nanoreactors (Figure 4a and b). After impregnating the nanoparticles in a tetrachloride aurate aqueous solution and heating at 80 °C for 17 min, small gold nanoparticles with a thermodynamically stable spherical shape were formed (Figure S4a). With the extending of reaction time, some of the small particles were dissolved and grew on large ones through the Ostwald ripening process (Figure S4b). The increase of particle diameter induced the decrease of surface energy. Thus, the effect of atomic packing in the lattices on the particle morphologies is dominated. Owing to hexagonal or cubic packing structure is most stable, and the surface structure prefers low index planes such as {111}, {100}, and {110}. After 80 min, one gold core with the shape of a triangle, prism, or cube is formed in one yolk−shell nanoparticle (Figure 4c). The UV−vis spectrum of the gold loaded yolk−shell nanoparticles showed two strong plasmon resonance bands at 577 and 633 nm, which is significantly redshifted compared to that of spherical gold particles, further indicating the formation of polyhedral gold nanoparticles in the yolk−shell spheres. The ICP-AES measurement showed that the gold in the composite materials was about 22.6%. The enclosed gold polyhedrons endowed the thioether-bridged yolk−shell mesoporous nanoparticles with unique photothermal ability. As shown in Figure 4e-g, the temperature of the gold polyhedron loaded nanoparticle suspension increased quickly to about 70 °C at a concentration of 1 mg mL−1 upon laser irradiation of 635 nm at 1.2 W cm−2 for 5 min. In strong contrast, no obvious temperature increasing was observed in the pure water under the same laser irradiation condition. The excellent heating ability and the mesoporous structure of the F

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moieties to give thiol groups and then connecting with Cy5.5-maleimide, near-infrared illuminated yolk−shell mesoporous nanoparticles can be successfully synthesized, which show great promise for in vitro and in vivo imaging.

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ASSOCIATED CONTENT

S Supporting Information *

TEM images of mesoporous nanoparticles with thioetherbridged frameworks synthesized with total precursor contents of 0.7 and 0.0875 mL and at TESPTS/TEOS volume ratios of 0.1/0.1 and 0.1/0. TEM image, XRD pattern, and UV−vis spectrum of gold nanoparticles from the reaction of TESPTS and HAuCl4. TEM images of gold loaded yolk−shell nanoparticles prepared by impregnating the thioether-bridged yolk−shell mesoporous nanoparticles in tetrachloride aurate aqueous solution for 17 and 34 min. Optical photo and fluorescence image of near-infrared illuminated yolk−shell mesoporous nanoparticles. In vivo imaging of nude mice before and after intravenous injection free Cy5.5-maleimide and Cy5.5 grafted yolk−shell mesoporous nanoparticles. This material is available free of charge via the Internet at http://pubs.acs.org.

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Figure 5. (a) Fluorescence confocal image of MCF-7 cells incubated with 100 μg/mL of the near-infrared illuminated yolk−shell mesoporous nanoparticles for 2 h at 37 °C, which is captured on an Olympus FV1000 LSCM under the Cy5.5 filter (λex = 635 nm, λem = 650−750 nm). (b) The corresponding bright-field confocal image and (c) the overlay image of (a) and (b). (d) In vivo imaging of a tumorbearing nude mouse by intratumorally injecting the near-infrared yolk−shell mesoporous nanoparticles using the Xenogen IVIS Lumina XR system (λex = 640 nm, λem = 705 nm).

AUTHOR INFORMATION

Corresponding Author

*Phone: 86 25 8086 0185. Fax: 86 25 8480 4659. E-mail: cjr. [email protected]. Author Contributions Δ

Z.T. and X.S. contributed equally to this work.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We greatly appreciate financial support from the National Key Basic Research Program of the PRC (2014CB744504 and 2011CB707700), the Major International (Regional) Joint Research Program of China (81120108013), the National Natural Science Foundation of China (81201175, 81371611, and 81401469), the Natural Science Foundation of Jiangsu Province (BK20130863), and the National Science Foundation for Postdoctoral Scientists of China (2013T60939 and 2012M521934). We especially appreciate Prof. Morgan A. McClure of Nanchong Professional Technic College and Qianqian Ni of Nanjing University for their assistance in revising of the manuscript.

(Figure 5d). Furthermore, in vivo imaging of nude mice was performed after intravenous injection of the near-infrared nanoparticles and free Cy5.5-maleimide (Figure S6). Upon intravenous injection, the fluorescence signal of free Cy5.5maleimide in the body was gradually decreased due to free dyes suffered from rapid blood/renal clearance. After 8 h, the signal disappeared, indicating that free Cy5.5-maleimide has been cleared. In contrast, the fluorescence signal of Cy5.5 grafted yolk−shell mesoporous nanoparticles in the body was first increased and retained up to 8 h, suggesting the Cy5.5 grafted nanoparticles have relatively longer retention. The in vivo imaging results suggested that the nanoparticles had excellent tissue penetration capability, and they are promising for various biomedical applications, such as tumor detection or drug delivery monitoring.

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4. CONCLUSIONS In summary, uniform yolk−shell mesoporous nanoparticles with thioether-bridged organosilica frameworks have been successfully prepared by hydrothermal treatment of mesostructured organic−inorganic hybrid nanospheres. The yolk−shell mesoporous nanoparticles have ultrahigh condensation degree, high surface area (400 m2 g−1), uniform pore size (2.0 nm), and large pore volume (0.67 cm3 g−1). Their diameter, core size, and shell thickness can be easily modulated by adjusting the reaction parameters. By using the thioether-bridged yolk−shell mesoporous nanoparticles as in situ nanoreactors, gold polyhedron loaded yolk−shell mesoporous nanoparticles can be conveniently prepared, which show strong plasmon resonance peaks at 577 and 633 nm and excellent photothermal efficiency. Furthermore, through breaking the thioether G

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