Reduced Graphene Oxide Sandwich

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Chemistry of Materials

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Synthesis of Mesoporous Silica/Reduced Graphene Oxide Sandwich–Like Sheets with Enlarged and “Funneling” Mesochannels Yupu Liu,† Wei Li,† Dengke Shen,† Chun Wang,† Xiaomin Li,† Manas Pal,† Renyuan Zhang,† Lei Chen,† Chi Yao,† Yong Wei,† Yuhui Li,† Yujuan Zhao,† Hongwei Zhu,† Wenxing Wang,† Ahmed Mohamed El–Toni,‡ § Fan Zhang,† and Dongyuan Zhao†* †

Department of Chemistry, Laboratory of Advanced Materials, Shanghai Key Lab of Molecular Catalysis and Innovative Materials, iChEM and State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, P. R. China ‡

King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia

§

Central Metallurgical Research and Development Institute, CMRDI, Helwan 11421, Cairo, Egypt

KEYWORDS: Mesoporous materials, graphene, sandwich–like nanosheet, mesochannels, drug delivery, photothermal therapeutic ABSTRACT: Here, we report the synthesis of reduced graphene oxide@mesoporous silica (denoted as rGO@mSiO2) sandwich–like sheets by an oil–water biphase stratification approach. The resultant rGO@mSiO2 nanosheets possess a uniform sandwich–like structure, ultrathin thickness (~ 50 nm), large aspect ratio, high surface area (~ 755 m2/g), and enlarged and tunable pore size (from 2.8 to 8.9 nm). Significantly, the mesochannels are oriented perpendicularly to graphene surfaces and shape like a funnel, which facilitates drug loading and releasing. The influences of the concentration of precursor, solvent, GO sheet, and reaction temperature on the formation of the sandwich–like rGO@mSiO2 nanosheets have been systematically investigated. The resultant nanosheets with a pore size of ~ 8.9 nm show the maximum loading capacity of bovine β–lactoglobulin (55.1 wt %). The protein releasing process in the simulated body fluid suggests that the release can be controlled from 20 to 60 h simply by adjusting the pore size. In addition, the degradability of rGO@mSiO2 nanosheets can be well controlled by tuning the pore size as well. Most importantly, the nanosheets exhibit a rapid photothermal heating under the near–infrared (NIR) irradiation. Therefore, the resultant nanosheets would have a hopeful prospect in large–molecule–weight drug delivery system, which have both the chemical and photothermal therapeutic functions.

targeting, tracking efficacy.12–23

INTRODUCTION Mesoporous silica has attracted growing interests due to their excellent properties including high porosities, large specific surface areas, low densities, tunable and large pore sizes, hydrophilic surfaces and good biocompatibilities, as a result, which shows promising applications in many areas of science and technology such as separation, adsorption, sensors, catalysis, optics and biomedicine.1–10 Particularly, in the biomedical applications, mesoporous silica with pore sizes matching the scale of drugs, enzymes, and/or proteins offers a flexible platform for drug delivery.11–15 Up to now, tremendous efforts have been devoted to synthesize multifunctional mesoporous silica composites with excellent magnetic, photothermal and/or luminescent properties for advanced drug delivery with

and/or

improving

therapeutic

Graphene with many interesting physical and chemical properties24–30 such as relatively low cost and biocompatibility has been extensively explored in the area of nanomedicine. More importantly, it has well been demonstrated that graphene exhibits strong optical absorption from visible to near–infrared (NIR) regions, making it a robust photothermal agent for effective tumor ablation.31–39 For example, Dai et al. have prepared poly(ethylene glycol)–coated reduced graphene oxide sheets, which appeared to be excellent NIR photothermal therapy agents for selective photoablation of U87MG cancer cells.40 Akhavan et al. have developed glucose– reduced graphene oxide (GO) sheets as a highly efficient NIR photothermal therapy of LNCaP prostate cancer 1

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cells.41 Nevertheless, due to their hydrophobic and inert structure, the implementation of graphene is greatly impeded by its poor water dispersion and low drug loading capacity when being chosen to perform the drug loading experiments in biomedium.17,40–45 Therefore, much work has been conducted to coat graphene with mesoporous silica, which can be used as a novel light– responsive drug delivery platform. Furthermore, the drug loading and releasing process would be facilitated when the mesochannels derived from silica layer's are vertically aligned. To date, many attempts such as external-field assisted methods46,47 by utilizing anisotropic external fields (e.g., air flow, electric, and magnetic fields), structural transformation48,49 of metal oxides (γ-Al2O3 and TiO2) frameworks from a 3D mesostructure during the thermal processes, confined effect50,51 in small space, and substrate templating growth strategies52–54 based on π–π or hydrophilic–hydrophobic interactions have been reported to prepare perpendicular mesopore channels. However, a few examples are demonstrated to prepare GO@mesoporous silica nanosheets with vertically oriented mesochannels. Unfortunately, the mesoporous silica coated graphene sheets reported previously still suffer from the limitation of small pore sizes (~ 3 nm), which can only deliver small drug molecules.17,55–59 Thus many proteins, enzymes and drugs with relatively large molecular sizes (4 to 9 nm) are still lack of applicability in chemotherapy and biocatalysis field.11,13,15,60

Materials. Cetyltrimethylammonium chloride (CTAC) solution (25 wt % in H2O) and triethanolamine (TEA) were purchased from Sigma–Aldrich (UK). Tetraethyl orthosilicate (TEOS), concentrated H2SO4, KNO3, KMnO4, HI aqueous solution (45 wt %) and ethanol were of analytical grade and purchased from Shanghai Chemical Corp. Graphite was purchased from Sigma–Aldrich. All chemicals were used as received without further purification. Deionized water was used for all experiments. Synthesis of Graphene Oxide (GO). GO was synthesized from graphite via a modified Hummers method. Briefly, in a 2–L three–necked round bottom flask, commercial graphite (5.0 g) was mixed with concentrated H2SO4 (115 mL) under an ice–water bath with a continuous mechanical stirring (250 rmp). KNO3 (2.5 g) and KMnO4 (15 g) were added very slowly (with a period more than 15 min) into the mixture. All the operations were carried out very slowly in a fume hood. The solution was allowed to stir in an ice–water bath for 2 h, then at 35 °C for 1 h. Afterwards, 115 mL of water was added to the flask. After 1 h, 700 mL of water was added. After another 15 min, the solution was removed from the oil bath and 50 mL of 30 % H2O2 were added to end the reaction. This suspension was stirred at room temperature for 5 min. The suspension was then repeatedly centrifuged and washed twice with 5 % HCl solution and then dialyzed for a week. Preparation of Reduced Graphene Oxide/Mesoporous Silica nanosheets (denoted by rGO@mSiO2). The rGO@mSiO2 nanosheets were achieved via an oil–water biphase stratification approach, by using cationic surfactant CTAC as the template, GO as the substrate, TEOS as the silica source, TEA as the catalyst and organic solvent (e.g., cyclohexane) as an emulsion agent. A typical synthesis of the sandwich nanocomposites was performed as following. 0.8 mg of GO was first dispersed in 12 mL of deionized water by sonication for 2 h to form a GO suspension. 8 ml of (25 wt %) CTAC solution and 0.048 mL of TEA were added into the GO suspension and sonicated for 0.5 h. Then, the mixture was transferred to a 75–mL round bottom flask and stirred gently at 60 °C for 1 h in an oil bath. 7 mL of (10 v/v %) TEOS in cyclohexane was carefully dropped into the above mixture under mild stirring at 60 °C. After that, the mixture was reacted under a constant temperature with continuous stirring for 3 h. The desired product was obtained by centrifugation and washing for several times with water and ethanol. Then, the collected product was dispersed in a ammonium nitrate (NH4NO3) ethanol solution (0.6 wt %) kept at 60 °C with vigorous stirring for 12 h to remove the template. The as– synthesized GO@mSiO2 nanosheets were obtained by centrifugation and washing for several times with water and ethanol. The rGO@mSiO2 nanosheets were formed by dispersing GO@mSiO2 nanosheets into HI aqueous solution (45 wt %) in a 50–mL round bottom flask that was placed in a thermostatted oil bath. After magnetic

Here, we report the synthesis of reduced graphene oxide@mesoporous silica (denoted as rGO@mSiO2) sandwich–like nanosheets with size–tunable and vertical funneling mesochannels by an oil–water biphase stratification approach (Scheme 1). In this case, graphene oxide (GO) nanosheets with in–plane hydroxy and epoxide functional groups were chosen as the substrate. This was accomplished by mixing GO with cetyltrimethylammonium chloride (CTAC, as a soft template) and triethanolamine (TEA, as a catalyst) in an aqueous solution as the bottom aqueous phase. The solution of tetraethyl orthosilicate (TEOS) in hydrophobic organic solvent served as the upper oil phase. The resultant rGO@mSiO2 nanosheets possess a uniform sandwich–like structure with vertically oriented “funneling” mesochannels, ultrathin thickness (~ 50 nm), large aspect ratio, uniform mesoporous structure, high surface area (~ 755 m2/g), enlarged and tunable pore size (from 2.8 to 8.9 nm). More importantly, the rGO@mSiO2 nanosheets show excellent performance towards large– molecule–weight protein loading (55.1 wt % for bovine β– lactoglobulin) and releasing (completed in 20 h), biodegradation, and a rapid photothermal heating under the near–infrared (NIR) irradiation. We believe that such novel two–dimensional (2D) nanosheets would have a hopeful prospect in multifunctional and large–molecule– weight drug (or enzyme, and protein) delivery system.

EXPERIMENTAL SECTION 2



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stirring for 2 h at 80 °C, the rGO@mSiO2 nanosheets were obtained by washing with water and ethanol, centrifugation, and drying. In addition, the influences of TEOS concentration, hydrophobic organic solvent, reaction temperature and GO concentration on the formation of the sandwich–like rGO@mSiO2 nanosheets were investigated under the same condition.

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under vacuum at 180 °C for at least 6 h prior to measurements. The Brunauer–Emmett–Teller (BET) method was utilized to calculate the specific surface areas using adsorption data in a relative pressure range from 0.05 to 0.25. Using the Barrett–Joyner–Halenda (BJH) model, the pore volumes and pore size distributions were derived from the adsorption branches of isotherms, and the total pore volumes (Vt) were estimated from the adsorbed amount at a relative pressure P/P0 of 0.995. Thermogravimetric analysis was conducted on a Mettler Toledo TGA–SDTA851 analyzer (Switzerland) from 35 to 900 °C under O2 with a heating rate of 5 °C/min. Transmission electron microscopy (TEM) experiments were conducted on a JEOL JEM–2100 F microscope (Japan) operated at 200 kV. The samples for the TEM measurements were suspended in ethanol and supported onto a holey carbon film on a Cu grid. Field–emission scanning electron microscopy (FESEM) images were taken on a Hitachi S–4800 microscope. The solution temperature was monitored by a thermal imaging camera (FLIR ThermaCAM A300).

Protein Loading and Release. The rGO@mSiO2 nanosheets with different pore sizes (8.9, 8.0, 5.0 and 2.8 nm denoted by rGO@mSiO2–1, rGO@mSiO2–2, rGO@mSiO2–3 and rGO@mSiO2–4, respectively) were chosen to examine the practical feasibility of the employed nanodrug delivery system. 5.0 mg of each kind of rGO@mSiO2 nanosheets was dispersed in 5.0 mL of the protein–buffer solution (1.0 mg cm–3), respectively. The mixtures were stirred gently (100 rmp) at 4 °C for 12 h in a bottle (30 × 50 mm) and centrifugated. Then, the concentration of the free protein in buffer solution could be accurately determined from the linear equation according to varied absorption intensity at 278 nm with UV–vis spectroscopy measurements. The loading capacity was calculated from the concentration of the free protein. The above rGO@mSiO2–2 and rGO@mSiO2–3 samples with the protein loading were respectively dispersed in Krebs solution at 37 °C under a mild stirring (100 rmp) for several hours in a bottle (30 × 50 mm). The release rates were determined by changing the concentration of the free protein in Krebs solution according to varied absorption intensity in 278 nm with UV–vis spectroscopy measurements. The degradation rate could be estimated from SEM and TEM images.

RESULTS AND DISCUSSION The formation process of uniform sandwich–like rGO@mSiO2 nanosheets and the detail growth process of vertical funneling mesochannels are illustrated in Scheme 1. Detailed experimental steps are described in the experimental section. The typical atomic force microscope (AFM) and thickness analysis images (Figure S1a, b) show that the GO nanosheets have a size range of 50–300 nm with a thickness of 0.8 ~ 1.2 nm, which ascertains the single–layer dispersion property of the GO solution.41 Field–emission scanning electron microscopy (FESEM) (Figure 1a) and transmission electron microscopy (TEM) images (Figure 1d) show that the sandwich–like rGO@mSiO2 samples are composed of various nanosheets with a size ranging from 50 to 300 nm (well fit with the size of original GO sheets) and uniform thickness of ~ 50 nm. No free silica nanoparticles or naked rGO sheets appear based on the observations of SEM and TEM visualizations. Remarkably, top–view FESEM and TEM images (Figure 1b, Figure 1e) reveal an ordered packing mesopores with a large pore size of ~ 8 nm over the entire silica layer without any mesochannel strips, suggesting that all mesopore channels are vertical to the surface. The SEM image of a torn rGO@mSiO2 sheet (Figure 1c) further discloses that the rGO nanosheets are conformably encapsulated by mesoporous silica layers. Interestingly, TEM images (Figure 1e, f) show that the inner surface of the mesoporous silica layer has a smaller pore size of ~ 3 nm than that of the outer surface (about 8 nm). The cross–section FESEM and TEM images (Figure 1g–i) clearly reveal that the sandwich–like structure in which the rGO sheets are uniformly coated by mesoporous silica layer (~ 25 nm in thickness). More importantly, one can clearly observe that the mesochannels are perpendicular to the surface and shape

Photothermal Irradiation. In order to determine the impact of sample concentrations on the photothermal efficiency, a series of rGO@mSiO2 solutions with different concentrations from 5 to 90 μg cm–3 were exposed to a laser radiation at 808 nm with a power density of 3 W cm– 2 . In addition, the rGO@mSiO2 solution (60 μg cm–3) was irradiated with different power densities to identify if the NIR power density had any influence on the final photothermal efficiency. The solution temperature was monitored by a thermal imaging camera (FLIR ThermaCAM A300). The samples GO, SiO2 and GO@mSiO2 corresponding to the rGO@mSiO2 concentration at 60 μg cm–3 were used as controls. Measurements and Characterization. Atomic force microscopy (AFM) measurements were taken using a Multimode Nano 4 in the tapping mode. The samples were deposited on a freshly cleaved mica surface. The small–angle X–ray scattering (SAXS) measurements were taken on a Nanostar U SAXS system (Bruker, Germany) using Cu Kα radiation (40 kV, 35 mA). Fourier–transform infrared spectroscopy (FT–IR) spectra were measured on a Fourier Transform Infrared Spectrometer (IRPrestige– 2.1). The UV–vis spectra were recorded on a UV–vis spectrometer (Jasco V–550) at 25 °C. Nitrogen sorption isotherms were measured at 77 K with a Micromeritcs Tristar 2420 analyzer. All of the samples were degassed 3


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like a funnel with a pore size of ~ 3 nm in bottom and 8

nm in up.

Scheme 1. Synthesis process of the sandwich–like rGO@mSiO2 nanosheets with enlarged and “funneling” mesochannels by an oil–water biphase stratification approach.

with the SEM and TEM results, while the pores size calculated from the desorption branch is ~ 7.3 nm. Again the adsorption branch values are observed to successively increase with relative pressure in a range from 0.05 to 0.85. These results imply a nonuniform cylindrical mesochannels having a “funneling” type structure.

Figure 1. FESEM (a–c) and TEM (d–f) images with different magnifications of the sandwich–like structured rGO@mSiO2 nanosheets prepared by an oil–water biphase stratification approach. Cross–section FESEM (d, e) and TEM (f) images of the sandwich–like rGO@mSiO2 nanosheets.

Figure 2. (a) SAXS pattern, (b) nitrogen adsorption/desorption isotherms and the corresponding pore size distributions (inset) of the sandwich–like rGO@mSiO2 nanosheets obtained by an oil–water biphase stratification approach.

The small–angle X–ray scattering (SAXS) pattern (Figure 2a) of the sandwich–like rGO@mSiO2 sheets shows a single scattering peak at ~ 0.65 nm–1, indicating a uniform meso-structure. Nitrogen adsorption/desorption isotherms of the sandwich–like rGO@mSiO2 nanosheets depict characteristic type IV curves (Figure 2b), further suggesting a uniform mesoporous structure. The capillary condensation step and hysteresis loop at around 0.45 < P/P0 < 0.80 is obviously observed, implying a narrow pore size distribution. The surface area and total pore volume are calculated to be about 713 m2 g–1 and 1.73 cm3 g–1, respectively. The pore size calculated by the Barrett– Joyner–Halenda (BJH) method using the adsorption branch is ~ 8.0 nm (Figure 2b, inset), which is consistent

TEM and corresponding elemental mapping images (Figure S2a–d) show the homogeneous dispersion of C, Si, and O elements in the sandwich–like rGO@mSiO2 nanosheets, further indicating that these nanosheets are encapsulated by mesoporous silica films. Fourier– transform infrared spectroscopy (FT–IR) spectra (Figure S3a) and thermog-ravimetric analysis (TGA) (Figure S3b) provide further proofs of the existence and reduction of GO in the rGO@mSiO2 sheets. The characteristic peaks at 1728 cm–1 can be assigned to the C=O stretching vibrations of carboxyl groups, 1631 cm–1 to aromatic C=C bonds, and 4



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1398 cm–1 to carboxy C–O bonds of GO sheets, respectively. The bands at 1080 and 800 cm–1 can be attributed to the stretching vibration of Si–O–Si bonds. A broad peak between 3000 and 3700 cm–1 associated with the hydroxyl groups of GO and mesoporous silica is observed. After HI acid reduction, the two bands at 1728 and 1398 cm–1 in the rGO@mSiO2 nanosheets are markedly reduced, clearly suggesting the reduction of GO. The broad peaks between 3000 and 3700 cm–1 are not obviously reduced after HI acid reduction because of the good retention of hydroxyl groups of mesoporous silica, which are favorable for drug delivery. TGA analysis of the sandwich–like GO@mSiO2 nanosheets (Figure S3b) shows a multistep weight loss and approximately 11.4 % main loss occurring in the temperature region from 200 to 600 °C (mainly from decomposition of graphene oxide). In comparison, the rGO@mSiO2 sheets present a ~ 8.7 % weight loss. More importantly, the degradation temperature shifts to ~ 600 °C. It further proves the nearly complete restoration of graphene by the HI acid reduction.

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sheets can be easily controlled from ~ 4.6 to 8.0 nm by changing the organic solvent in the upper oil phase (Table 1). The temperature is another important factor for the funnel mesopore silica layer coating. SEM images show that the low temperature (30 °C) results in rare mesoporous silica deposition on the surface of rGO nanosheets (Figure S6a), because of the low polymerization rate for the silicate oligomers in aqueous solution. When the temperature increased to 45 °C, uniform rGO@mSiO2 nanosheets were obtained (Figure S6b, d). Considering the boiling point of cyclohexane, the highest temperature was fixed at 70 °C. SEM images (Figure S6c) show that the pore size of the mesoporous silica layers is slightly disrupted, which is consistent with the SAXS results (Figure S6d). The influence of GO concentration in the bottom aqueous solution was also investigated. TEM images (Figure S7a) show that monodispersed mesoporous silica nanospheres with center–radial mesopore channels can be obtained under the same conditions without GO, which is consistent with our previous results.15 When GO nanosheets (0.02 mg cm–3) was added into the synthetic solution, the GO@mSiO2 sheets with uniform mesochannels were obtained, which were combined with mesoporous silica nanospheres as by–product (Figure S7b). It is mainly due to the competitive process of the heterogeneous nucleation and growth with the homogeneous ones.61 When the GO concentration was set in the range of 0.04 – 0.10 mg cm–3, the GO@mSiO2 nanosheets without impurity could be easily prepared with uniform mesopore channels (Figure S7c, d). These results clearly suggest that the silicate oligomers preferentially grow and polymerize on GO sheets, mainly because the oxygen functional groups of the GO sheets can serve as active sites for heterogeneous nucleation. When the GO concentration increased to 0.15 mg cm–3, TEM images (Figure S7e) revealed that the mesoporous silica nanoparticles were randomly dispersed on the GO sheets and partially naked surfaces of the GO sheets could be observed due to the insufficient silica sources. These results indicate that the optimum GO concentration is critical to get uniform sandwich–like rGO@mSiO2 nanosheets.

Here, the effect of TEOS concentration in cyclohexane was first investigated on the resultant rGO@mSiO2 nanosheets. When a 6.6 v/v % of TEOS/cyclohexane solution was chosen as the upper oil phase, FESEM and TEM images show that the obtained rGO@mSiO2 sandwich–like nanosheets (denoted by rGO@mSiO2–1) have a large pore size of ~ 8.9 nm (Figure S4a, d). However, when the concentration of TEOS in cyclohexane was increased to 20 v/v %, the rGO@mSiO2 nanosheets with a small pore size of about 5.0 nm (Figure S4b, e) are obtained (denoted by rGO@mSiO2–3). Further increasing the TEOS concentration to 40 v/v % results in a relatively smaller pore size of ~ 2.8 nm (denoted by rGO@mSiO2–4) (Figure S4c, f). The nitrogen adsorption/desorption isotherms, pore size distribution curves, and SAXS patterns (Figure S4g–i) of the resultant rGO@mSiO2 nanosheets further confirm the uniform mesoporous structures with pore sizes of ~ 8.9, 5.0, and 2.8 nm, respectively. The concentration–dependent experiments disclose that the pore sizes can be well controlled from ~ 2.8 to 8.9 nm by adjusting TEOS concentration (Table 1). In addition, the effect of organic solvent in the upper oil phase was also investigated. When decahydronaphthalene was used as the solvent (10 v/v % TEOS) in the upper oil phase, uniform rGO@mSiO2–5 nanosheets could be obtained with a pore size of ~ 6.5 nm (Figure S5a, c). The SEM image (Figure S5a) shows that the mesopore channels of the silica layer are perpendicular to the rGO surface. By using 1–octadecene as the organic solvent, the small–pore sized mesoporous silica layers (~ 4.6 nm) can be formed (Figure S5b, d). The texture properties can be further verified by the nitrogen adsorption/desorption isotherms, pore size distribution cures, and SAXS patterns (Figure S5e–g). These results further suggest that the pore sizes of the rGO@mSiO2

In order to further understand the growth process of funnel mesoporous silica on GO nanosheets, time– dependent experiments were conducted. Compared to the GO nanosheet (Figure 3a), TEM image (Figure 3b) reveals that a large number of ultradispersed micelles were grown on the nanosheets after 20 min. The presence of silicate/CTA+ composites is further unraveled by the energy–dispersive X–ray (EDX) analysis (Figure 3f). With the reaction, the micelles would gradually assemble into uniform ordered mesostructures with a uniform micelle size of ~ 3 nm (Figure 3c). After 90 min, a uniform mesoporous silica layer was obtained on the surface of GO sheets with an opened pore size of ~ 5 nm (Figure 3d). 5


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Further prolonging time led to the formation of mesoporous silica with enlarged opened pore sizes of ~ 8 nm (Figure 3e, Figure 2b). The nitrogen adsorption/desorption isotherms and pore size distribution curves (Figure S8, Figure 2b) of the resultant rGO@mSiO2 nanosheets under different times (40, 90, and 180 min) after the addition of TEOS solution further confirm the enlarged and “funneling” mesochannels with pore sizes of ~ 2.7, 5.3, and 8.0 nm, respectively.

GO/surfactant/inorganic species could get in touch with the hemiemulsion micelles repeatedly, resulting in the formation of “funneling” mesochannels owing to the pore-expanding effect of organic solvent (Scheme 1d, e).15,64–67 Free silicate oligomers also continuously polymerized in the gap between neighboring micelles to form self-adaptive pore walls (Scheme 1e). After solvent extraction and reduction, the rGO@mSiO2 sheets with enlarged mesochannels oriented perpendicularly to the rGO substrate were obtained (Scheme 1f). In this case, the upper oil phase not only behaves as the storage medium for silica precursors, which can slow down the hydrolysis rate of silicate species, but also acts as the pore-expanding agent. Hence it makes the overall heterogeneous nucleation and growth of mesostructures on GO sheets controllable in the bottom aqueous solution.15,61,64–67 In addition, the formation of hemimicelles (oligomers/surfactant/organic solvent molecules) is a critical step, which can act as the enlarged building blocks for the final “funneling” mesochannels. Because both the lower silica resource concentration and smaller– molecule–weight organic solvent would make the interfacial curvature of micelles to be larger.12,15,64–67 Combined with the mutual extrusion of adjacent mesochannels, ordered “funneling” mesostructures would be eventually obtained with the lowest interface energy on GO sheets after step-by-step growth.

Figure 3. TEM images of the rGO@mSiO2 nanosheets prepared via an oil–water biphase stratification approach under different times after the addition of TEOS solution (a–f): (a) 0 min, (b) 20 min, (c) 40 min, (d) 90 min, (e) 180 min and (f) the energy–dispersive X–ray (EDX) analysis of the products after 20 min reaction. All scale bars in TEM images are 100 nm.

Based on the above results, we have proposed a possible mechanism for the growth of the mesoporous silica sheets on GO nanosheets (Scheme 1). In our biphase system, a heterogeneous oil–water biphase reaction system was formed after the addition of TEOS/cyclohexane solution (Scheme 1a). First, TEOS in the upper organic solvent gradually diffused to the biphase interface, slowly hydrolyzed and polymerized into negatively charged silicate oligomers, which would drive into the bottom aqueous solution owing to the gravity and hydrophilic/hydrophobic interactions.15,62–67 Simultaneously, hemiemulsion micelles were supposed to generate at the biphase interface as a result of the lowest interface energy.15,64–66 Some of negatively charged silicate oligomers could then gather around CTA+ head groups of the hemiemulsion micelles, forming oligomers/surfactant /organic solvent hemiemulsion micelles (Scheme 1b), which would drive into the bottom aqueous solution and serve as new building blocks for subsequent mesostructure growth.15,64–66 In the bottom aqueous solution, silicate oligomers and CTAC molecules could co-assemble into micelles, then nucleating on the surface of GO nanosheets (Scheme 1b, c).17,55–59 Remaining silicate oligomers in aqueous solution would be further bound to the micelles and polymerized in the gap between neighboring micelles and GO sheets to form pore walls (Scheme 1c, d).17,55–59,61 As the reaction continues, the

Figure 4. (a) Protein release curve of the sandwich–like rGO@mSiO2–2 nanosheets in Krebs solution at 37 °C. (b–f) TEM images of the rGO@mSiO2–2 nanosheets at different degradation intervals: (b) 0 h, (c) 4 h, (d) 12 h, (e) 16 h and (f) 20 h. The sample is prepared via oil–water biphase stratification approach and all scale bars in TEM images are 100 nm.

The drug loading and releasing of the rGO@mSiO2 nanosheets has been studied by using large protein bovine β–lactoglobulin (MW = 36,754, Size: 5.65 × 4.96 × 3.78 nm) as an example. The acetic acid–sodium acetate buffer solution with a pH value of 5.0 was used for the entire drug loading process, which is between the isoelectric point (pI) of bovine β–lactoglobulin (~ 6.0) and the silanol on the surface of mesochannels of the rGO@mSiO2 sandwich–like nanosheets (~ 3.0). It means 6



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Table 1. Textural properties and protein loading capacities of the samples prepared by an oil–water biphase stratification approacha Samples

TEOS concentration

Hydrophobic organic solvent

(v/v %)

Pore size (nm)

area (m g )

Pore vol3 −1 ume (cm g )

BET surface 2

−1

Protein loading (wt %)

rGO@mSiO2–1

cyclohexane

6.6

8.9

755

1.92

55.1

rGO@mSiO2–2

cyclohexane

10

8.0

713

1.73

48.1

rGO@mSiO2–3

cyclohexane

20

5.0

512

1.08

22.4

rGO@mSiO2–4

cyclohexane

40

2.8

424

0.93

12.2

rGO@mSiO2–5

decahydronaphthalene

10

6.5

617

1.49

––

rGO@mSiO2–6

1–octadecene

10

4.6

451

0.97

––

a

All the samples were synthesized under the same condition and the corresponding pore sizes were determined from the adsorption branch based on the BJH model.

that the surface of the mesochannels appears to be negatively charged and bovine β–lactoglobulin positively charged in the buffer solution. Thus, bovine β– lactoglobulin can be strongly adsorbed on the mesochannel surfaces of the rGO@mSiO2 nanosheets via electrostatic interaction. The protein loading measurements (Figure S9) show that the sample rGO@mSiO2–4 sheets (pore size: ~ 2.8 nm) exhibits a loading capacity of 12.2 wt %. When the pore size of the rGO@mSiO2 nanosheets is enlarged to close to or larger than that of the protein, a high loading capacity can be achieved by absorption under the same condition. The rGO@mSiO2–3 (pore size: ~ 5.0 nm), rGO@mSiO2–2 (pore size: ~ 8.0 nm), and rGO@mSiO2–1 (pore size: ~ 8.9 nm) nanosheets show the protein loading as 20.8, 48.1 and 55.1 wt%, respectively. These results disclose a clear dependence of protein–loading capacity on the pore size. The protein releasing process (Figure 4a) suggests that the rGO@mSiO2–2 nanosheets show a rapid release in the simulated body fluid (Krebs solution), which can be completed within 20 h. In contrast, the rGO@mSiO2–3 sheets show a slow release (~ 60 h) (Figure S10a). Such a large difference implies that the drug release rate can be controlled by changing the pore size of the mesoporous silica layers. In addition, the TEM images (Figure 4b–f and Figure S10b–f) also suggest that with the release of the protein in Krebs solution, the rGO@mSiO2 nanosheets can be gradually degraded. Similar to the protein releasing, a large difference between the rGO@mSiO2–2 and rGO@mSiO2–3 nanosheets in the degradation process is also observed. The rGO@mSiO2–2 nanosheets show a rapid degradation (~ 20 h) (Figure 4b– f). After 4 h, the mesopore channels are destroyed and obvious defects can be observed on the sheet surface (Figure 4c). Almost all of the mesochannels are disrupted and the surface becomes rough and jagged after 12 h (Figure 4d). With the degradation time further increasing, only some silica particles appear on the surface of rGO sheets (Figure 4e). After 20 h, only naked rGO nanosheets

Figure 5. (a) Temperature change curves of the graphene oxide (GO), mesoporous SiO2, GO@mSiO2 and rGO@mSiO2 (prepared via the oil–water biphase stratification approach) solutions exposed to a laser radiation at 808 nm with a power density of 3 W cm–2. The GO and GO@mSiO2 solution have the same graphene concentration with the rGO@mSiO2 solution (60 μg cm–3). The SiO2 solution has the same silica concentration to the rGO@mSiO2 solution (60 μg cm–3); (b) Photothermal heating curves of the rGO@mSiO2 solution (60 μg cm–3) at various power intensities; (c) Thermal images of the solution irradiated with 808–nm laser at 3 W cm–2 for 7 min: (c1) SiO2; (c2) GO; (c3) GO@mSiO2; (c4) rGO@mSiO2 (5 μg cm–3); (c5) rGO@mSiO2 (30 μg cm–3); (c6) rGO@mSiO2 (60 μg cm–3); (c7) rGO@mSiO2 (90 μg cm–3); (c8) 1 W cm–2 (c9) 2W cm–2. 7


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can be observed (Figure 4f), indicating that the degradation is almost completed. TEM images (Figure S10b–f) show that the sandwich–like rGO@mSiO2–3 nanosheets take a longer time (~ 60 h) to finish the degradation process. The results suggest that well– controlled pore size of the rGO@mSiO2 samples can help to realize intelligent on–demand drug–release and nano– carrier degradation.

ASSOCIATED CONTENT Supporting Information The AFM topography image of the GO sheets; FT–IR spectra and TGA curves of GO@mSiO2 and rGO@mSiO2 sheets; SEM and TEM images; Nitrogen adsorption–desorption isotherms, pore size distribution curves and SAXS patterns of the products obtained with different reaction conditions; UV–vis spectra of the bovine β–lactoglobulin solution; protein release curves of the rGO@mSiO2–3 sheets and TEM images of the rGO@mSiO2–3 sheets at different degradation intervals; UV–vis absorption curves of GO, GO@mSiO2 and rGO@mSiO2. This material is available free of charge via the Internet at http://pubs.acs.org.

UV–vis spectra (Figure S11) show that the sandwich–like rGO@mSiO2 nanosheets have higher optical absorbance in the NIR region than the GO and GO@mSiO2, respectively, further confirming the efficient reduction of graphene oxide by HI acid. To study the potential of the rGO@mSiO2 nanosheets in photothermal therapy upon NIR laser irradiation, the rGO@mSiO2–2 solution (60 μg cm–3) was tested as the model, which was exposed to an NIR laser with a power intensity of 3 W cm–2 at 808 nm. The temperature of the rGO@mSiO2–2 solution rapidly increases and reaches 45 °C within 4 min, indicating the effective photothermal effect. Figure 5C shows that the temperature of the rGO@mSiO2–2 solution gradually changes from 26 to 50 °C at every interval (0.5 minute). While all control solutions (GO, mesoporous silica, and GO@mSiO2 solution) remain the temperature below 31 °C even after 7 min (Figure 5a). The excellent photothermal effect can be attributed to the efficient reduction of GO nanosheets, more importantly, in which the resultant rGO nanosheets are not aggregated owing to the perfect protection of silica.32,40,56 Furthermore, the rGO@mSiO2 solution exhibits a concentration–dependent (from 5 to 90 μg cm–3) and laser power intensity–dependent (from 1 to 3 W cm–2) photothermal heating effect (Figure 5b). It illustrates that the temperature can be facilely controlled, thus the sandwich–like rGO@mSiO2 nanosheets can be used as a promising candidate for photothermal therapy.

AUTHOR INFORMATION Corresponding Author *E–mail: [email protected]

ACKNOWLEDGMENT This work was supported by the State Key Basic Research Program of the PRC (2012CB224805 and 2013CB934104), Shanghai Sci. & Tech. Committee (14JC1400700), Shanghai Nanotech Promotion Centre (0852nm00100), NSF of China (grant no. 21210004) and the authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding this work through Research Group No. RG–1435–002.

REFERENCES (1) Zhao, D. Y.; Feng, J. L.; Huo, Q. S.; Melosh, N.; Fredrickson, G. H.; Chmelka, B. F.; Stucky, G. D. Triblock Copolymer Syntheses of Mesoporous Silica with Periodic 50 to 300 Angstrom Pores. Science 1998, 279, 548–552. (2) Li, X. M.; Zhou, L.; Wei, Y.; El–Toni, A. M.; Zhang F.; Zhao, D. Y. Anisotropic Growth–Induced Synthesis of Dual– Compartment Janus Mesoporous Silica Nanoparticles for Bimodal Triggered Drugs Delivery. J. Am. Chem. Soc. 2014, 136, 15086– 15092. (3) Han, L.; Xu, D. P.; Liu, Y.; Ohsuna, T.; Yao, Y.; Jiang, C.; Mai, Y. Y.; Cao, Y. Y.; Duan, Y. Y.; Che, S. A. Synthesis and Characterization of Macroporous Photonic Structure that Consists of Azimuthally Shifted Double–Diamond Silica Frameworks. Chem. Mater. 2014, 26, 7020–7028. (4) Parlett, C. M. A.; Wilson, K.; Lee, A. F. Hierarchical Porous Materials: Catalytic Applications. Chem. Soc. Rev. 2013, 42, 3876– 3893. (5) Chen, Z.; Jiang, Y. B.; Dunphy, D. R.; Adams, D. P.; Hodges, C.; Liu, N. G.; Zhang, N.; Xomeritakis, G.; Jin, X. Z.; Aluru, N. R.; Gaik, S. J.; Hillhouse, H. W.; Brinker, C. J. DNA Translocation through an Array of Kinked Nanopores. Nat. Mater. 2010, 9, 667–675. (6) Dunphy, D. R.; Sheth, P. H.; Garcia, F. L.; Brinker, C. J. Enlarged Pore Size in Mesoporous Silica Films Templated by Pluronic F127: Use of Poloxamer Mixtures and Increased Template/SiO2 Ratios in Materials Synthesized by Evaporation– Induced Self–Assembly. Chem. Mater. 2015, 27, 75–84. (7) Wei, J.; Yue, Q.; Sun, Z. K.; Deng, Y. H.; Zhao, D. Y. Synthesis of Dual–Mesoporous Silica Using Non–Ionic Diblock Copolymer and Cationic Surfactant as Co–Templates. Angew. Chem. Int. Ed. 2012, 51, 6149–6153.

CONCLUSIONS In summary, large pore mesoporous silica coated graphene nanosheets have been successfully prepared by an oil–water biphase stratification approach. The resultant rGO@mSiO2 nanosheets possess a uniform sandwich–like structure with vertically oriented mesochannels, ultrathin thickness (~ 50 nm), large aspect ratio, uniform mesoporous structure and high surface area (~ 755 m2/g). Interestingly, the mesochannels are observed to have an enlarged and tunable pore size (2.8 to 8.9 nm) with a funnel–like shape. This method is very simple and reproducible. More importantly, the sandwich–like rGO@mSiO2 nanosheets show excellent performance towards large molecule–weight protein loading (55.1 wt % for bovine β–lactoglobulin) and fast releasing (completed in 20 h), pore size-dependent biodegradation, and rapid photothermal heating to a high temperature under the NIR irradiation. Such novel nanosheets pave a promising way to advanced cancer therapeutic and biocatalysis.

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Magnetic Functionalization and Gene Delivery. Adv. Mater. 2014, 26, 4947–4953. (23) Terentyuk, G.; Panfilova, E.; Khanadeev, V.; Chumakov, D.; Genina, E.; Bashkatov, A.; Tuchin, V.; Bucharskaya, A.; Maslyakova, G.; Khlebtsov, N.; Khlebtsov, B. Gold Nanorods with a Hematoporphyrin–Loaded Silica Shell for Dual–Modality Photodynamic and Photothermal Treatment of Tumors in Vivo. Nano Res. 2014, 7, 325–337. (24) Kim, S.; Nham, J.; Jeong, Y. S.; Lee, C. S.; Ha, S. H.; Park, H. B.; Lee, Y. J. Biomimetic Selective Ion Transport through Graphene Oxide Membranes Functionalized with Ion Recognizing Peptides. Chem. Mater. 2015, 27, 1255–1261. (25) Gao, L.; Ni, G. X.; Liu, Y.; Liu, B.; Castro–Neto, A. H.; Loh, K. P. Face–to–Face Transfer of Wafer–Scale Graphene Films. Nature 2014, 505, 190–194. (26) Su, C. L.; Tandiana, R.; Balapanuru, J.; Tang, W.; Pareek, K.; Nai, C. T.; Hayashi, T.; Loh, K. P. Tandem Catalysis of Amines Using Porous Graphene Oxide. J. Am. Chem. Soc. 2015, 137, 685– 690. (27) Sun, W.; Wang, L. D.; Wu, T. T.; Wang, M.; Yang, Z. Q.; Pan, Y. Q.; Liu, G. C. Inhibiting the Corrosion–Promotion Activity of Graphene. Chem. Mater. 2015, 27, 2367–2373. (28) Li, W.; Wang, F.; Feng, S. S.; Wang, J. X.; Sun, Z. K.; Li, B.; Li, Y. H.; Yang, J. P.; Elzatahry, A. A.; Xia, Y. Y.; Zhao, D. Y. Sol– Gel Design Strategy for Ultradispersed TiO2 Nanoparticles on Graphene for High–Performance Lithium Ion Batteries. J. Am. Chem. Soc. 2013, 135, 18300–18303. (29) Li, W.; Wang, F.; Liu, Y. P.; Wang, J. X.; Yang, J. P.; Zhang, L. J.; Elzatahry, A. A.; Al–Dahyan, D.; Xia, Y. Y.; Zhao, D. Y. General Strategy to Synthesize Uniform Mesoporous TiO2/Graphene/ Mesoporous TiO2 Sandwich–Like Nanosheets for Highly Reversible Lithium Storage. Nano Lett. 2015, 15, 2186– 2193. (30) Lipatov, A.; Wymore, B. B.; Fursina, A.; Vo, T. H.; Sinitskii A.; Redepenning, J. G. Electropolymerization of Poly(phenylene oxide) on Graphene as a Top–Gate Dielectric. Chem. Mater. 2015, 27, 157–165. (31) Feng, L. Y.; Wu, L.; Qu, X. G. New Horizons for Diagnostics and Therapeutic Applications of Graphene and Graphene Oxide. Adv. Mater. 2013, 25, 168–186. (32) Li, M.; Yang, X. J.; Ren, J. S.; Qu, K. G.; Qu, X. G. Using Graphene Oxide High Near–Infrared Absorbance for Photothermal Treatment of Alzheimer's Disease. Adv. Mater. 2012, 24, 1722–1728. (33) Yang, K.; Feng, L. Z.; Shi, X. Z.; Liu, Z. Nano–Graphene in Biomedicine: Theranostic Applications. Chem. Soc. Rev. 2013, 42, 530–547. (34) Li, X. L.; Wang, X. R.; Zhang, L.; Lee, S. W.; Dai, H. J. Chemically Derived, Ultrasmooth Graphene Nanoribbon Semiconductors. Science 2008, 319, 1229–1232. (35) Dreyer, D. R.; Park, S.; Bielawski, C. W.; Ruoff, R. S. The Chemistry of Graphene Oxide. Chem. Soc. Rev. 2010, 39, 228– 240. (36) Liu, Z.; Robinson, J. T.; Sun, X. M.; Dai, H. J. PEGylated Nanographene Oxide for Delivery of Water–Insoluble Cancer Drugs. J. Am. Chem. Soc. 2008, 130, 10876–10877. (37) Zhang, L. M.; Xia, J. G.; Zhao, Q. H.; Liu, L. W.; Zhang, Z. J. Functional Graphene Oxide as a Nanocarrier for Controlled Loading and Targeted Delivery of Mixed Anticancer Drugs. Small 2010, 6, 537–544. (38) Dong, H. F.; Ding, L.; Yan, F.; Ji, H. X.; Ju, H. X. The Use of Polyethylenimine–Grafted Graphene Nanoribbon for Cellular Delivery of Locked Nucleic Acid Modified Molecular Beacon for Recognition of MicroRNA. Biomaterials 2011, 32, 3875–3882.

(8) Li, W.; Yue, Q.; Deng, Y. H.; Zhao, D. Y. Ordered Mesoporous Materials Based on Interfacial Assembly and Engineering. Adv. Mater. 2013, 25, 5129–5152. (9) Li, W.; Zhao, D. Y. An Overview of the Synthesis of Ordered Mesoporous Materials. Chem. Commun. 2013, 49, 943–946. (10) Huang, X. D.; Zhou, L.; Yu C. Z.; Zhao, D. Y. Self– Assembly of Monodispersed Silica Nano–Spheres with a Closed– Pore Mesostructure. J. Mater. Chem. 2012, 22, 11523–11528. (11) Zhou, Z.; Hartmann, M. Progress in Enzyme Immobilization in Ordered Mesoporous Materials and Related Applications. Chem. Soc. Rev. 2013, 42, 3894–3912. (12) Yang, Y. N.; Niu, Y. T.; Zhang, J.; Meka, A. K.; Zhang, H. W.; Xu, C.; Lin, C. X.; Yu, M. H.; Yu, C. Z.; Biphasic Synthesis of Large–Pore and Well–Dispersed Benzene Bridged Mesoporous Organosilica Nanoparticles for Intracellular Protein Delivery. Small 2015, DOI: 10.1002/smll.201402779. (13) Wu, M. Y.; Meng, Q. S.; Chen, Y.; Du, Y. Y.; Zhang, L. X.; Li, Y. P.; Zhang, L. L.; Shi, J. L. Large–Pore Ultrasmall Mesoporous Organosilica Nanoparticles: Micelle/Precursor Co– templating Assembly and Nuclear–Targeted Gene Delivery. Adv. Mater. 2015, 27, 215–222. (14) He, Q. J.; Zhang, J. M.; Shi, J. L.; Zhu, Z. Y.; Zhang, L. X.; Bu, W. B.; Guo, L. M.; Chen, Y. The Effect of PEGylation of Mesoporous Silica Nanoparticles on Nonspecific Binding of Serum Proteins and Cellular Responses. Biomaterials 2010, 31, 1085– 1092. (15) Shen, D. K.; Yang, J. P.; Li, X. M.; Zhou, L.; Zhang, R. Y.; Li, W.; Chen, L.; Wang, R.; Zhang, F.; Zhao, D. Y. Biphase Stratification Approach to Three–Dimensional Dendritic Biodegradable Mesoporous Silica Nanospheres. Nano Lett. 2014, 14, 923–932. (16) Liu, J. J.; Wang, C.; Wang, X. J.; Wang, X.; Cheng, L.; Li, Y. G.; Liu Z. Mesoporous Silica Coated Single–Walled Carbon Nanotubes as a Multifunctional Light–Responsive Platform for Cancer Combination Therapy. Adv. Funct. Mater. 2015, 25, 384– 392. (17) Wang, Y.; Wang, K. Y.; Zhao, J. F.; Liu, X. G.; Bu, J.; Yan, X. Y.; Huang, R. Q. Multifunctional Mesoporous Silica–Coated Graphene Nanosheet Used for Chemo–Photothermal Synergistic Targeted Therapy of Glioma. J. Am. Chem. Soc. 2013, 135, 4799– 4804. (18) Song, G. S.; Wang, Q.; Wang, Y.; Lv, G.; Li, C.; Zou, R. J.; Chen, Z. G.; Qin, Z. Y.; Huo, K. K.; Hu, R. G.; Hu, J. Q. A Low– Toxic Multifunctional Nanoplatform Based on Cu9S5@mSiO2 Core–Shell Nanocomposites: Combining Photothermal– and Chemotherapies with Infrared Thermal Imaging for Cancer Treatment. Adv. Funct. Mater. 2013, 23, 4281–4292. (19) Liu, X. W.; Tao, H. Q.; Yang, K.; Zhang, S.; Lee, S. T.; Liu, Z. Optimization of Surface Chemistry on Single–walled Carbon Nanotubes for in Vivo Photothermal Ablation of Tumors. Biomaterials 2011, 32, 144–151. (20) Chen, Y.; Chen, H. R.; Zhang, S. J.; Chen, F.; Zhang, L. X.; Zhang, J. M.; Zhu, M.; Wu, H. X.; Guo, L. M.; Feng, J. W.; Shi, J. L. Multifunctional Mesoporous Nanoellipsoids for Biological Bimodal Imaging and Magnetically Targeted Delivery of Anticancer Drugs. Adv. Funct. Mater. 2011, 21, 270–278. (21) Zhang, Z. J.; Wang, L. M.; Wang, J.; Jiang, X. M.; Li, X. H.; Hu, Z. J.; Ji, Y. L.; Wu, X. C.; Chen, C. Y. Mesoporous Silica– Coated Gold Nanorods as a Light–Mediated Multifunctional Theranostic Platform for Cancer Treatment. Adv. Mater. 2012, 24, 1418–1423. (22) Niu, D. C.; Liu, Z. J.; Li, Y. S.; Luo, X. F.; Zhang, J. Y.; Gong, J. P.; Shi, J. L. Monodispersed and Ordered Large–Pore Mesoporous Silica Nanospheres with Tunable Pore Structure for

9


Page 11 of 11

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(39) Wang, Y. H.; Wang, H. G.; Liu, D. P.; Song, S. Y.; Wang, X.; Zhang, H. J. Graphene Oxide Covalently Grafted Upconversion Nanoparticles for Combined NIR Mediated Imaging and Photothermal/Photodynamic Cancer Therapy. Biomaterials 2013, 34, 7715–7724. (40) Robinson, J. T.; Tabakman, S. M.; Liang, Y. Y.; Wang, H. L.; Casalongue, H. S.; Vinh, D.; Dai, H. J. Ultrasmall Reduced Graphene Oxide with High Near–Infrared Absorbance for Photothermal Therapy. J. Am. Chem. Soc. 2011, 133, 6825–6831. (41) Akhavan, O.; Ghaderi, E.; Aghayee, S.; Fereydooni, Y.; Talebi, A. The Use of a Glucose–Reduced Graphene Oxide Suspension for Photothermal Cancer Therapy. J. Mater. Chem. 2012, 22, 13773–13781. (42) Hu, S. H.; Chen, Y. W.; Hung, W. T.; Chen, I. W.; Chen, S. Y. Quantum–Dot–Tagged Reduced Graphene Oxide Nanocomposites for Bright Fluorescence Bioimaging and Photothermal Therapy Monitored In Situ. Adv. Mater. 2012, 24, 1748–1754. (43) Bao, H. Q.; Pan, Y. Z.; Ping, Y.; Sahoo, N. G.; Wu, T. F.; Li, L.; Li, J.; Gan, L. H. Chitosan–Functionalized Graphene Oxide as a Nanocarrier for Drug and Gene Delivery. Small 2011, 7, 1569– 1578. (44) Hu, W. B.; Peng, C.; Lv, M.; Li, X. M.; Zhang, Y. J.; Chen, N.; Fan, C. H.; Huang, Q. Protein Corona–Mediated Mitigation of Cytotoxicity of Graphene Oxide. ACS Nano 2011, 5, 3693–3700. (45) Li, D.; Muller, M. B.; Gilje, S.; Kaner, R. B.; Wallace, G. G. Processable Aqueous Dispersions of Graphene Nanosheets. Nat. Nanotechnol. 2008, 3, 101–105. (46) Walcarius, A.; Sibottier, E.; Etienne, M.; Ghanbaja, J. Electrochemically Assisted Self-Assembly of Mesoporous Silica Thin Films. Nat. Mater. 2007, 6, 602–608. (47) Yamauchi, Y. Field-Induced Alignment Controls of Onedimensional Mesochannels in Mesoporous Materials. J. Ceram. Soc. Jpn. 2013, 121, 831–840. (48) Yamaguchi, A.; Uejo, F.; Yoda, T.; Uchida, T.; Tanamura, Y.; Yamashita, T.; Teramae. N. Self-Assembly of a Silica– Surfactant Nanocomposite in a Porous Alumina Membrane. Nat. Mater. 2004, 3, 337–341. (49) Lu, Q. Y.; Gao, F.; Komarneni, S.; Mallouk, T. E. Ordered SBA-15 Nanorod Arrays Inside a Porous Alumina Membrane. J. Am. Chem. Soc. 2004, 126, 8650–8651. (50) Wu, C. W.; Ohsuna, T.; Kuwabara, M.; Kuroda, K. Formation of Highly Ordered Mesoporous Titania Films Consisting of Crystalline Nanopillars with Inverse Mesospace by Structural Transformation. J. Am. Chem. Soc. 2006, 128, 4544–4545. (51) Oveisi, H.; Jiang, X. F.; Imura, M.; Nemoto, Y.; Sakamoto, Y.; Yamauchi, Y. A. Mesoporous γ-Alumina Film with Vertical Mesoporosity: The Unusual Conversion from a Im3m Mesostructure to Vertically Oriented γ-Alumina Nanowires. Angew. Chem. Int. Ed. 2011, 50, 7410–7413. (52) Yamauchi, Y.; Nagaura, T.; Ishikawa, A.; Chikyow, T.; Inoue, S. Evolution of Standing Mesochannels on Porous Anodic Alumina Substrates with Designed Conical Holes. J. Am. Chem. Soc. 2008, 130, 10165–10170. (53) Richman, E. K.; Brezesinski, T.; Tolbert. S. H. Vertically Oriented Hexagonal Mesoporous Films Formed through Nanometre-scale Epitaxy. Nat. Mater. 2008, 7, 712–717. (54) Hara, M.; Nagano, S.; Seki, T. π–π Interaction-Induced Vertical Alignment of Silica Mesochannels Templated by a Discotic Lyotropic Liquid Crystal. J. Am. Chem. Soc. 2010, 132, 13654–13656. (55) Wang, Z. M.; Wang, W. D.; Coombs, N.; Soheilnia, N.; Ozin, G. A. Graphene Oxide–Periodic Mesoporous Silica Sandwich Nanocomposites with Vertically Oriented Channels. ACS Nano 2010, 4, 7437–7450.

(56) Yang, S. B.; Feng, X. L.; Wang, L.; Tang, K.; Maier, J.; Mullen, K. Graphene–Based Nanosheets with a Sandwich Structure. Angew. Chem. Int. Ed. 2010, 49, 4795–4799. (57) Lin, Y. H.; Wu, L.; Huang, Y. Y.; Ren, J. S.; Qu, X. G. Positional Assembly of Hemin and Gold Nanoparticles in Graphene– Mesoporous Silica Nanohybrids for Tandem Catalysis. Chem. Sci. 2015, 6, 1272–1276. (58) Tang, H. Y.; Shen, S.; Guo, J.; Chang, B. S.; Jiang, X. G.; Yang, W. L. Gold Nanorods@mSiO2 with a Smart Polymer Shell Responsive to Heat/Near–Infrared Light for Chemo– Photothermal Therapy. J. Mater. Chem. 2012, 22, 16095–16103. (59) Li, W.; Zhao, D. Y. Extension of the Stöber Method to Construct Mesoporous SiO2 and TiO2 Shells for Uniform Multifunctional Core–Shell Structures. Adv. Mater. 2013, 25, 142–149. (60) Lobovkina, T.; Jacobson, G. B.; Gonzalez–Gonzalez, E.; Hickerson, R. P.; Leake, D.; Kaspar, R. L.; Contag, C. H.; Zare, R. N. In Vivo Sustained Release of siRNA from Solid Lipid Nanoparticles. ACS Nano 2011, 5, 9977–9983. (61) Li, W.; Yang, J. P.; Wu, Z. X.; Wang, J. X.; Li, B.; Feng, S. S.; Deng, Y. H.; Zhang, F.; Zhao, D. Y. A Versatile Kinetics– Controlled Coating Method to Construct Uniform Porous TiO2 Shells for Multifunctional Core–Shell Structures. J. Am. Chem. Soc. 2012, 134, 11864–11867. (62) Edler K. J.; Yang, B. Formation of Mesostructured Thin Films at the Air–liquid Interface. Chem. Soc. Rev. 2013, 42, 3765– 3776. (63) Wu, S. H.; Mou, C. Y.; Lin, H. P. Synthesis of Mesoporous Silica Nanoparticles. Chem. Soc. Rev. 2013, 42, 3862–3875. (64) Yang, J. P.; Chen, W. Y.; Shen, D. K.; Wei, Y.; Ran, X. Q.; Teng, W.; Fan, J. W.; Zhang, W. X.; Zhao, D. Y. Controllable Fabrication of Dendritic Mesoporous Silica–Carbon Nanospheres for Anthracene Removal. J. Mater. Chem. A 2014, 2, 11045–11048. (65) Yang, J. P.; Shen, D. K.; Zhou, L.; Li, W.; Fan, J. W.; ElToni, A. M.; Zhang, W. X.; Zhang, F.; Zhao, D. Y. Mesoporous Silica-Coated Plasmonic Nanostructures for Surface-Enhanced Raman Scattering Detection and Photothermal Therapy. Adv. Healthcare Mater. 2014, 3, 1620–1628. (66) Yang, J. P.; Shen, D. K.; Wei, Y.; Li, W.; Zhang, F.; Kong, B.; Zhang, S. H.; Teng, W.; Fan, J. W.; Zhang, W. X.; Dou, S. X.; Zhao, D. Y. Monodisperse Core-Shell Structured Magnetic Mesoporous Aluminosilicate Nanospheres with Large Dendritic Mesochannels. Nano Res. 2015, DOI: 10.1007/s12274–015–0758–2. (67) Carcouët, C. C. M. C.; van de Put, M. W. P.; Mezari, B.; Magusin, P. C. M. M.; Laven, J.; Bomans, P. H. H.; Friedrich, H.; Esteves, A. C. C.; Sommerdijk, N. A. J. M.; van Benthem, R. A. T. M.; de With, G. Nucleation and Growth of Monodisperse Silica Nanoparticles. Nano Lett. 2014, 14, 1433–1438.

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Yupu Liu, Wei Li, Dengke Shen, Chun Wang, Xiaomin Li, Manas Pal, Renyuan Zhang, Lei Chen, Chi Yao, Yong Wei, Yuhui Li, Yujuan Zhao, Hongwei Zhu, Wenxing Wang, Ahmed Mohamed El–Toni, Fan Zhang, and Dongyuan Zhao* Synthesis of Mesoporous Silica/Reduced Graphene Oxide Sandwich–Like Sheets with Enlarged and “Funneling” Mesochannels

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Reduced Graphene Oxide Sandwich

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