Fabrication of PDEAEMA-Coated Mesoporous Silica Nanoparticles

Jul 6, 2010 - He , E.; Yue , C. Y.; Simeon , F.; Zhou , L. H.; Too , H. P.; Tam , K. C. J. Biomed. Mater. Res. 2009, 91A, 708– 718. [Crossref], [CAS...
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J. Phys. Chem. C 2010, 114, 12481–12486

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Fabrication of PDEAEMA-Coated Mesoporous Silica Nanoparticles and pH-Responsive Controlled Release Jiao-Tong Sun, Chun-Yan Hong,* and Cai-Yuan Pan CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, UniVersity of Science and Technology of China, Hefei, Anhui 230026, People’s Republic of China ReceiVed: May 2, 2010; ReVised Manuscript ReceiVed: June 10, 2010

Mesoporous silica nanoparticles (MSNs) are considered for potential scaffoldings in drug delivery due to their good biocompatibility and large pore volume, and it is the focus to find a suitable gatekeeper for the mesopores. In this paper, a reliable and versatile method of surface-initiated atom transfer radical polymerization (SI-ATRP) has been employed to prepare the hybrid poly(2-(diethylamino)ethyl methacrylate)-coated MSNs (MSN-PDEAEMA). The resultant hybrid nanoparticles with pH-sensitive polymer shell and MSN core were characterized by a series of techniques including high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, and nitrogen adsorption isotherms. The pHresponsive PDEAEMA brushes anchored on MSNs could serve as a switch to control the opening and closing of the pores. Release of guest molecules was conducted at different pHs, and the results showed rapid release in acidic aqueous solution but very little leakage in alkaline solution. By adjusting the pH of the solution repeatedly, the release of encapsulated molecules could be switched on and off at will. We envision that this nanosystem should have potential applications in sited release of anticancer drug and gene delivery. 1. Introduction The discovery of hexagonally ordered mesoporous silica by Mobil Corp in 1992 is a breakthrough in materials chemistry.1,2 Mesoporous silica materials have attracted widespread interest due to their extremely high surface areas (700-1200 m2/g), easily accessible and uniformly sized pores (2-50 nm), and good biocompatibility.3,4 After appropriate surface modification, the resulting products are found to have extensive applications in catalysis,5,6 sorbents,7-9 dental materials,10 drug release,11-15 and gene delivery.16,17 Among these applications, one of the most interesting studies is to control drug release based on the opening or closing of the pores. For realizing this purpose, “smart” caps are incorporated in the pore outlets or the external surface of mesoporous silica nanoparticles (MSNs). Hybrid nanoparticles can be prepared commonly by either covalent grafting techniques or physical absorption. Lin et al. employed magnetic nanoparticles,18 cadmium sulfide,13 and gold nanoparticles16 as gatekeepers to regulate the release of guest molecules encapsulated in the pores of MSNs by the introduction of the disulfide-reducing trigger or by cleavage of a disulfide linkage under physiological conditions. Although some of these delivery systems achieved zero release in the absence of stimuli, irreversibility of opening and closing of the pores would limit effective use of these delivery systems. Kim and co-workers accomplished controlled release of guest molecules from mesoporous silica particles using a pH-sensitive polypseudorotaxane motif.19 Another pH-responsive nanovalve, which relies on the ion-dipole interaction between cucurbit[6]uril and bisammonium stalks attached on the surface of MCM-41, was also studied.20 In addition, pH- and photoswitched release of the entrapped guest has been achieved based on interaction between a saccharide derivative riveted on the pore outlets of MSNs and boronic acid functionalized gold caps.21 The pH* To whom correspondence should be addressed. E-mail: hongcy@ ustc.edu.cn.

controlled nanovalves mentioned above can realize reversible opening and closing of the nanopores, but the synthesis of the molecular or supermolecular gates is relatively complex. Stimuli-responsive polymers are grafted onto the internal or external surface of mesoporous silica materials to regulate the transport of encapsulated molecules. When a stimulus, such as a change of pH, temperature, or light, is applied, their physicalchemical properties change as a response, and further these “smart” polymers could control access to the pores. As one of the most reported temperature-responsive polymers, poly(Nisopropylacrylamide) has been grafted to the mesoporous silica materials by atom transfer radical polymerization (ATRP),22-24 reversible addition-fragmentation chain transfer (RAFT) polymerization25,26 and chemical coupling reaction.27 An abrupt phase transition upon heating at its lower critical solution temperature makes it well-conducted in simulated drug release.22-24,27 Apart from the simple procedure of fabrication, these nanocarriers could also control the drug release repeatedly. It seems that smart polymers should be better as a nanovalve for controlled drug release. Recently, our group grafted a poly(acrylic acid) (PAA) shell onto the exterior surface of MSNs via RAFT polymerization, producing a novel nanodevice with MSN as a carrier and the pH-responsive PAA nanoshell as a smart nanovalve.28 The PAA nanoshell could regulate uptake and release of guest molecules. Xu et al. coated poly(methacrylic acid) (PMAA) onto MSNs by copolymerization of MAA with vinyl triethoxysilane.29 Both of these pH-responsive nanocontainers have similar release behavior. In alkaline solution, the pores are open and the drug is released owing to extending of the polymer chains, while the compact polymer layers block the pores and confine the drug in the pores in acidic medium. In practice, the external pH of cancerous tissues is usually lower than that of the surrounding normal tissues due to a high rate of glycolysis in tumor tissues, that is, the surface of cancerous cells is acidic.30 To eliminate the side effect of chemotherapy, it is demanded

10.1021/jp103982a  2010 American Chemical Society Published on Web 07/06/2010

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that more drugs should be released at the proper site. So the acid-triggered release system, which releases the drugs under acidic conditions and ceases the release at neutral or alkaline pH, should be useful in practical applications, especially in anticancer drug delivery. Poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) is too hydrophobic to be water-soluble at neutral or alkaline pH, and the polymer chains in their uncharged form are collapsed; while in acidic solution it is soluble as a weak cationic polyelectrolyte and the protonated chains adopt an extended conformation.31-34 Herein, PDEAEMA was selected to functionalize the MSNs through surface-initiated ATRP of DEAEMA. The pKa for protonated PDEAEMA is around pH 7-8,34 which means that this polyelectrolyte deprotonates almost completely above pH 8. The release behaviors of the guest molecules from this nanocarrier were investigated at three selected pHs and the results showed that release of the guest molecules could be well controlled. So this nanocomposite delivery system should have potential applications in targeted drug release and gene delivery. 2. Experimental Methods 2.1. Materials. 2-(Diethylamino)ethyl methacrylate (DEAEMA, Aldrich, 99%) was purified by passing it through an alumina column for removal of inhibitor, followed by vacuum distillation. Toluene (Sinopharm Chemical Reagent Co, 99%) was refluxed over sodium for 24 h and then distilled prior to use. 3-Aminopropyltriethoxysilane (APTES, Aldrich, 98%), tetraethyl orthosilicate (TEOS), N-cetyltrimethylammonium bromide (CTAB, Aldrich, 99%), and N,N,N′,N′,N′′- pentamethyldiethylenetriamine (PMDETA, Aldrich) were used as received. CuBr (Sinopharm Chemical Reagent Co. 98%) was purified by stirring in glacial acetic acid, washed with methanol, and then dried in a vacuum oven. All other reagents were of analytical grade and used as received. 2.2. Synthesis of Amino-Modified MSN (MSN-NH2). MSNs were synthesized with the sol-gel method according to the literature.35 CTAB (1.00 g, 2.7 × 10-3 mol) was first dissolved in 500 mL of distilled water, aqueous solution of NaOH (2.00 M, 4 mL) was added, and then the solution temperature was raised to 80 °C. TEOS (5.00 mL, 2.5 × 10-2 mol) was then introduced dropwise to the surfactant solution. After the addition was completed, the mixture was stirred for another 4 h. The white precipitates formed were filtered, washed with methanol, and dried under vacuum at 40 °C overnight. Amino modification of the silica surface was performed by suspending the obtained nanoparticles (1.5 g) in a solution of APTES (2.6 mmol, 0.6 mL) in dry toluene (30.0 mL) and the resulting mixture was heated under reflux for 24 h under nitrogen atmosphere. The nanoparticles were collected by filtration, washed thoroughly with toluene, and dried under vacuum. Removal of the CTAB template was carried out as follows. The amino-functionalized MSNs (1.5 g) were suspended in MeOH (160 mL), to which a concentrated aqueous solution of HCl (12 M, 9 mL) was added, and the mixture was heated under reflux for 24 h. The MSN-NH2 were collected by filtration, washed thoroughly with MeOH, and dried in vacuum oven for 24 h. 2.3. Synthesis of MSN-Supported ATRP Initiator (MSNBr). MSN-NH2 (1.0 g), anhydrous THF (25.0 mL), and triethylamine (1.4 mL, 10 mmol) were added into a 100 mL flask, and then 2-bromo-2-methylpropionyl bromide (1.2 mL, 10 mmol) in 5 mL of anhydrous THF was added dropwise into the mixture at 0 °C for 30 min. The resulting mixture was stirred for 3 h at 0 °C and then at room temperature for 48 h. The

Sun et al. solid was then separated by filtration and washed three times with 100 mL of THF. The obtained product was redispersed in 20 mL of THF by ultrasonic processing, filtered, and washed three times to remove any adsorbed impurity. The MSN-Br was collected and dried overnight under vacuum at 40 °C. 2.4. Synthesis of PDEAEMA-Coated MSN (MSN-PDEAEMA). Typically, MSN-Br (100.0 mg), CuBr (36 mg, 0.250 mmol), PMDETA (43.5 mg, 0.250 mmol), DEAEMA (1.388 g, 7.5 mmol), and methanol (6.0 mL) were placed in a 20 mL dry flask, which was then sealed with a rubber plug. The solution was degassed by three freeze-pump-thaw cycles, and then placed in a thermostatted oil bath at 70 °C for 50 h. The polymerization was stopped by opening the polymerization tube to air. To ensure that no ungrafted polymer or free reagents were mixed in the product, the mixture was washed with THF by centrifugation (10 000 rpm) ten times; MSN-PDEAEMA was obtained after dried overnight under vacuum. 2.5. Dye Loading and Release Studies. The loading of rhodamine B (RhB) inside the mesopores of MSN-PDEAEMA was achieved as follows. The MSN-PDEAEMA (75 mg) was added in 25 mL aqueous solution of RhB (8.4 × 10-5 M, pH ) 4) and stirred for 14 h at room temperature. Then MSNPDEAEMA loaded with RhB was isolated by centrifugation at 10 000 rpm, washed extensively with alkaline water (pH ) 8) to remove the RhB adsorbed at the surface of MSN-PDEAEMA until the maximum emitting light intensity of the supernatant liquid was close to zero, and dried under vacuum. The release study was conducted as follows. Three aliquots (10 mg) of the RhB-loaded MSN-PDEAEMA were soaked in 25 mL of aqueous solutions at different pH (pH ) 2, 4, and 8, respectively) and stirred at the same rate in the centrifugation tubes at ambient temperature. At the predetermined time intervals, the mixture was centrifugated, and 2 mL of the supernatant liquids were withdrawn to record the luminescence spectrum. The liquids were then poured back into the tubes. 2.6. Retrieving the Grafted PDEAEMA from MSNPDEAEMA.36,37 MSN-PDEAEMA (10 mg) was dispersed in 3 mL of THF in a PTFE vessel, 0.5 mL of HF (40 w%, aq) was added, and the solution was stirred for 12 h at room temperature. The solution was neutralized with aqueous solution of sodium carbonate and dialyzed against deionized water using a dialysis membrane with a molecular weight cut off (MWCO) of 3500 Da for 2 days. Water was removed by freeze-drying, and then the recovered PDEAEMA was subjected to GPC analysis. 2.7. Characterization. Fourier transform infrared (FT-IR) spectra were recorded on a Bruker VECTOR-22 IR spectrometer. High-resolution transmission electron microscopy (HRTEM) images were recorded on a JEOL 2010 transmission electron microscope operated at an accelerating voltage of 200 kV. Powder XRD patterns were recorded on a Philips X′ Pert PRO SUPER X-ray diffractometer system with a Cu KR radiation source. Thermal gravimetric analyses (TGA) were conducted on a Perkin-Elmer Diamond TG/DTA Instruments with a heating rate of 10 °C/min in a nitrogen flow. Nitrogen adsorption isotherms were measured on an ASAP 2020 micromeritics porosimeter at 77 K using a 10 s equilibrium interval. The specific surface area was determined using the BET (Brunauer-Emmett-Teller) method and the pore size distribution was computed using the BJH (Barret-Joyner-Halenda) model. The total pore volume was calculated from the amount adsorbed at a relative pressure of 0.99. The hydrodynamic diameter of the MSN-PDEAEMA was measured with a Malvern Zetasizer Nano ZS-90 instrument at a series of different pH at

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SCHEME 1: Synthetic Route of PDEAEMAFunctionalized MSNs

Figure 1. HRTEM images of the MSNs (A,B) and MSN-PDEAEMA (C,D). All scale bars are 100 nm.

room temperature by dynamic light scattering. Luminescence spectra were recorded on a Shimadzu RF5301-PC spectrafluorophotometer. The molecular weight and molecular weight distribution of the polymers were measured on a Waters 150C gel permeation chromatography (GPC) equipped with microstyragel columns (500, 103, and 104 Å) and RI 2414 detector at 30 °C. Molecular weights were calibrated based on polystyrene standards. THF was used as an eluent at a flow rate of 1.0 mL/min. 3. Results and Discussion 3.1. Preparation of MSN-PDEAEMA. The MSN-PDEAEMA was fabricated according to Scheme 1. MSNs were synthesized with a base-catalyzed sol-gel method. Although in the modification of template-removed MSNs with APTES the external surface is more easily accessible and is functionalized predominantly over the internal mesopore surface,38 MSNs were still modified with APTES before removing the template molecules to evade functionalization in the internal surface of the pores. The template molecules inside the mesopores were then removed by washing with acidic solution in methanol.39,40 The MSN-Br was prepared by reaction of amino groups in MSN-NH2 with 2-bromo-2-methylpropionyl bromide, and then it was used in the ATRP of DEAEMA to obtain MSNPDEAEMA. HRTEM images of MSNs and MSN-PDEAEMA are presented in Figure 1. The resulting MSNs by a sol-gel process have an average diameter of about 100 nm and almost uniform pore size (Figure 1A,B). In comparison with MSNs, a rimlike polymer nanoshell can be observed clearly around the exterior surface of the silica nanoparticles as shown in Figure 1C,D. Meanwhile, the parallel stripes in the core area indicate that polymerization of DEAEMA do not destroy the mesoporous structure of the nanoparticles. The powder X-ray diffraction (XRD) is applied to characterize the structure of MSNs derivates (Figure 2). Three well-resolved reflection peaks (100), (110), and (200), the characteristic diffraction pattern of hexagonal MCM-41-type mesoporous silicas, are clearly observed in the XRD patterns of MSN-NH2, MSN-Br, and MSN-PDEAEMA. It indicates that the parallel cylindrical channel-like mesoporous structure of the MSN material is unaltered in the following

Figure 2. Powder XRD patterns of MSN-NH2 (a), MSN-Br (b), and MSN-PDEAEMA (c).

amidation reaction and the polymerization of DEAEMA on the surface of MSNs. Owing to the less contrast between the polymers and the pores, the diffraction peaks in MSNPDEAEMA are weaker than the corresponding peaks in MSN-NH2.27,41-43 The FT-IR spectroscopy is employed to provide direct identification of chemical groups in MSN-NH2, MSN-Br, and MSN-PDEAEMA (Figure 3). Amino-modification of MSNs is confirmed by a new band at around 1530 cm-1, a typical absorption peak of NH2 present on the surface of MSNs (Figure 3a). The absorption peak at 1540 cm-1 (Figure 3b) is ascribed to N-H bending vibration of the resultant amide group, indicating the attachment of 2-bromo-2-methylpropionyl group to the silica surface, and the absorption band at 1650 cm-1 ascribing to the stretching vibration of CdO is covered up by the bending O-H bands of adsorbed water. After polymerization of DEAEMA on the surface of MSNs, a new absorption peak at 1731 cm-1 in Figure 3c, which corresponds to the stretching vibration of ester carbonyl group in the PDEAEMA, can be observed. Besides, an intense increase of the adsorption peak at around 2950 cm-1 (νC-H) appears in contrast with Figure 3b. The thermogravimetric analysis of MSN-NH2, MSN-Br, and MSN-PDEAEMA was performed after these samples were dried under vacuum at 40 °C for 24 h. The results in Figure 4 show

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Figure 3. FT-IR spectra of MSN-NH2 (a), MSN-Br (b), and MSNPDEAEMA (c).

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Figure 5. GPC trace of the PDEAEMA cleaved from MSNPDEAEMA.

TABLE 1: Mesopore parameters of MSN-NH2 and MSN-PDEAEMA sample

SBET/m2g-1 a

DBJH/Åb

VP/cm3g-1 c

MSN-NH2 MSN-PDEAEMA

822.3 11.1

40.2

0.83 0.14

d

a

Surface area. b Average pore diameter. c Pore volume. d Mesopores were not accessible to nitrogen gas.

Figure 4. TGA curves for MSN-NH2 (a), MSN-Br (b), and MSNPDEAEMA (c).

that the weight losses of MSN-NH2, MSN-Br, and MSNPDEAEMA are 20.6, 29.9, and 64.6%, respectively, when the samples are heated to 800 °C. There is 9.3% difference of the weight loss between MSN-NH2 and MSN-Br at 800 °C. The graft density of initiating group on the surface of MSNs is calculated to be 0.78 mmol per gram of MSN-Br. The difference of weight loss between MSN-Br and MSN-PDEAEMA is 34.7%. It is obviously proved that PDEAEMA is successfully grafted on the surface of MSNs. To measure the molecular weight of the polymer on MSNs, the PDEAEMA was cleaved from the silicas. The polymer obtained after neutralized and dialyzed against deionized water was subjected to GPC analysis, and the result in Figure 5 showed that the number-average molecular weight (Mn) of PDEAEMA was 23 600 and the polydispersity index was 1.14. Lin et al. confirmed that the polymerization took place exclusively on the exterior surface of the MSNs when the MSNs were functionalized before washing the template away.25 Therefore, the subsequent reactions should not affect the mesopore structures. We employ the nitrogen adsorption/ desorption method to measure the pore structures of MSN-NH2 and MSN-PDEAEMA, and the results are summarized in Table 1. The specific surface area is 822.3 m2/g for MSN-NH2, but only 11.1 m2/g for MSN-PDEAEMA. The BET isotherm of MSN-NH2 exhibits the characteristic Type IV adsorption/ desorption pattern in Figure 6. The BJH pore size distribution of MSN-NH2 is narrow as shown in Figure 6 insert and the pore size is about 2.6 nm. But the BET isotherm of MSNPDEAEMA in Figure 7 demonstrates that the mesopores were inaccessible to nitrogen gas and in the BJH analysis all pores

Figure 6. Adsorption/desorption isotherm for MSN-NH2. Insert is BJH pore size distribution plot of the MSN-NH2.

are bigger than 10 nm (not shown), which might be interstices between these nanoparticles. It seems impossible that ATRP of DEAEMA takes place on internal surface of the mesopores because ATRP initiating groups exist exclusively on the exterior surface of the silicas. Thus it is reasonable to presume that the compact polymer layers on the surface of MSNs prevent penetration of the nitrogen. 3.2. pH-Responsive Behaviors of MSN-PDEAEMA. To examine the pH-dependent volume phase transition of the PDEAEMA shell, 0.1 mg/mL of MSN-PDEAEMA suspensions at different pH were measured by dynamic light scattering. The pH dependence of hydrodynamic diameter (Dh) of MSNPDEAEMA is shown in Figure 8. The Dh increases with the decrease of pH value. In acidic environment PDEAEMA brushes are partly or entirely protonated and become positively charged polyelectrolyte. The electrostatic repulsions and strong chainsolvent interactions44 make the polymer chains stretch, which lead to a larger Dh. However, in neutral and alkaline conditions, PDEAEMA brushes are deprotonated and become hydrophobic,

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Figure 9. The relationship of concentration of the released RhB with time at different pH values. Figure 7. Adsorption/desorption isotherm for MSN-PDEAEMA.

Figure 8. pH dependence of hydrodynamic diameter of MSNPDEAEMA.

so they are limited to available spaces where they are grafted from. Meanwhile, polymer chain-chain interactions are stronger than chain-solvent interactions, and polymer chains are prone to aggregate together to result in a smaller Dh. Armes et al. reported that PDEAEMA-grafted silica particles remained stable below pH 6 but flocculated in neutral/alkaline media.34 Probably, the concentration of suspensions in our experiment is so dilute that aggregation of the MSN-PDEAEMA does not occur. 3.3. pH-Dependent Release Studies. As a simulated drug, the hydrophilic RhB was loaded in the matrix of MSNPDEAEMA by introducing dry MSN-PDEAEMA to an aqueous solution of RhB. After the RhB-loaded MSN-PDEAEMA was washed adequately and vacuum-dried, it was placed in aqueous solution at different pH and stirred at a constant rate. At the predetermined time intervals, MSN-PDEAEMA was separated by centrifugation and the fluorescence of the supernatant fluid was measured, and then the liquid was poured back to maintain the total volume of the suspension. On the basis of the calibration curves of fluorescent intensity changed with the concentration of RhB at different pH, the fluorescent intensities were converted to the concentrations. The relationships of concentration of the released RhB with time at different pH are shown in Figure 9. The equilibrium concentration of released RhB at pH ) 8 is only about 10% of that at pH ) 2. It indicates that at pH ) 8 the mesopores are blocked by the collapsed polymer chains and RhB molecules are confined in the pathway of the pores. It is inevitable that the RhB confined in the outer layer of polymer diffuses gradually into the solution under

Figure 10. Release profile of RhB loaded in MSN-PDEAEMA nanocontainers with pH of the release medium alternately changed between 8 and 2 at ambient temperature.

stirring and it takes 9 h to reach the equilibrium. At pH ) 2 the PDEAEMA chains are protonated and become positively charged polyelectrolyte. The polymer chains stretch highly in the open state and almost do not hinder the release of RhB, so it takes only 4 h that the fluorescent intensity of the solution levels off. At pH ) 4 the curve levels off after 5 h, and the equilibrium concentration of RhB is a little less than that at pH ) 2. Because the polymer chains are less stretched than those at pH ) 2, the release of guest molecules is held up partly. The concentration of RhB released at the equilibrium depends on pH of the medium, so this pH-responsive polymer shell could control the drug release by changing pH of the solution. To investigate whether the release of RhB from this nanosystem could be repeated by altering pH of the release medium or not, 5 mg of the RhB-loaded MSN-PDEAEMA was soaked in 10 mL of aqueous solutions (pH ) 8) and stirred at ambient temperature. After every 0.5 h, the mixture was centrifugated and 3 mL of the supernatant liquid was withdrawn to record the luminescence spectrum and then was restituted. After 1.5 h, the whole supernatant liquid was replaced by 10 mL of aqueous solution (pH ) 2). The same procedure was repeated three times at pH 2. Figure 10 shows the release profile of RhB from MSNPDEAEMA with pH of the release medium alternately changed between 2 and 8. It indicates that the release of the mesoporeentrapped guest can be switched on and off at will. The property of acid-triggered release makes MSN-PDEAEMA a potential site-specific drug delivery system. In theory, when the blood circulation time of this delivery system in vivo is longer, more drugs could be released within the efficient region (e.g.,

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cancerous tissues). Polyethylene glycol (PEG) has been approved to increase the plasma half-life dramatically and reduce liver accumulation in mice.45 Moreover, it is reported that PDEAEMA-b-PEG copolymer exhibits low toxicity under certain conditions and could serve as a nonviral DNA delivery system.46 Once this nanosystem was PEGylated covalently, it should have satisfying release behavior in vivo. The corresponding work is underway. 4. Conclusions In summary, a novel pH-sensitive nanosystem based on mesoporous silica nanoparticles has been successfully prepared by employing SI-ATRP of DEAEMA. The tertiary amine in PDEAEMA is easy to get a proton to form quaternary ammonium and the polymer adopts the coil (soluble) conformation in acidic solution; while in the neutral or alkaline solution it is in the collapsed (insoluble) state due to the hydrophobic interaction of polymer chains. So PDEAEMA grafted on MSNs could act as a good gatekeeper to control access to the pores via a pH-dependent open-close mechanism, which is confirmed by the well-controlled release of RhB from the mesopores through adjusting pH of the solution. On the other hand, the weak acidity of cancerous tissues makes this acid-triggered release system probably suitable for controlled release of anticancer drugs. This nanodevice should have potential applications in site-selected drug release and gene delivery. Acknowledgment. This research was supported by National Natural Science Foundation of China (Nos. 20674077 and 20974103), Program for New Century Excellent Talents in University (NCET-08-0520), and the Fundamental Research Funds for the Central Universities. References and Notes (1) Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J. C.; Beck, J. S. Nature 1992, 359, 710–712. (2) Beck, J. S.; Vartuli, J. C.; Roth, W. J.; Leonowicz, M. E.; Kresge, C. T.; Schmitt, K. D.; Chu, C. T.-W.; Olson, D. H.; Sheppard, E. W.; McCullen, S. B.; Higgins, J. B.; Schlenker, J. L. J. Am. Chem. Soc. 1992, 114, 10834–10843. (3) Vallet-Regı´, M.; Ruiz-Gonza´lez, L.; Izquierdo-Barba, I.; Gonza´lezCalbet, J. M. J. Mater. Chem. 2006, 16, 26–31. (4) Stein, A.; Melde, B. J.; Schroden, R. C. AdV. Mater. 2000, 12, 1403–1419. (5) Clark, J. H.; Macquarrie, D. J. Chem. Commun. 1998, 853–860. (6) Jana, S.; Dutta, B.; Bera, R.; Koner, S. Inorg. Chem. 2008, 47, 5512–5520. (7) Liu, J.; Feng, X.; Fryxell, G. E.; Wang, L.-Q.; Kim, A. Y.; Gong, M. AdV. Mater. 1998, 10, 161–165. (8) Feng, X.; Fryxell, G. E.; Wang, L.-Q.; Kim, A. Y.; Liu, J.; Kemner, K. M. Science 1997, 276, 923–926. (9) Zhao, X. S.; Lu, G. Q. J. Phys. Chem. B 1998, 102, 1556–1561. (10) Samuel, S. P.; Li, S.; Mukherjee, I.; Guo, Y.; Patel, A. C.; Baran, G.; Wei, Y. Dent. Mater. 2009, 25, 296–301. (11) Barbe, C.; Bartlett, J.; Kong, L.; Finnie, K.; Lin, H. Q.; Larkin, M.; Calleja, S.; Bush, A.; Calleja, G. AdV. Mater. 2004, 16, 1959–1966. (12) Zhang, L.; Qiao, S.; Jin, Y.; Cheng, L.; Yan, Z.; Lu, G. Q. AdV. Funct. Mater. 2008, 18, 3834–3842.

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