通过空间限制电流取代制造金纳米笼核壳结构介孔二氧化硅,产物用

1、 Chemistry of Materials Article Figure 6. (A Photothermal curves of H2O and the Au-nanocage mSiO2PNIPAM (50 g mL1 under NIR laser irradiation (808 nm, 1 W/cm2 as a function of time. (B DOX release curves from the AunanocagemSiO2PNIPAM nanocarrier in PBS buer at pH 7.4 and pH 5, with or without the N

2、IR laser irradiation. (C Viability of HeLa cells with dierent concentration of carrier, DOX, and carrier + DOX, with or without the laser irradiation at 808 nm. (D Optical microscopy images of Trypan-blue-stained HeLa cells of carrier and Carrier+DOX with or without the laser irradiation at the conc

3、entration of 50 g mL1 (all scale bars are 50 m. indeed provide an eective photothermal conversion. Therefore, we adopted 50 g mL1 as the typical concentration to investigate the cancer therapy eciency of the nanocarriers. The DOX molecules, which is a well-studied anticancer drug, can be eciently lo

4、aded into the carrier with a capacity of 23.5 wt %. The NIR-stimulus in vitro drug release behaviors of DOX loaded in the carrier was performed in phosphate buer saline (PBS solution at dierent pH values. Only 7.5% and 18.4% DOX are released within 8 h at the pH 7.4 and pH 5, respectively (see Figur

5、e 6B. However, burst release was observed upon NIR irradiation and, subsequently, the rate slowed after the laser was switched o. After initial NIR irradiation for 5 min (1 W/cm2, 808 nm, the DOX release was signicantly increased from 1.2% to 10.4% at pH 7.4, and from 1.7% to 15% at pH 5. The cumula

6、tive release of DOX reached 32.8% and 78.9% within 8 h at pH 7.4 and pH 5.0, respectively, which are values that are signicantly higher than those without NIR irradiation (7.5% and 18.4% for pH 7.4 and pH 5, respectively (see Figure 6B. The stepwise triggered rapid DOX release with NIR irradiation i

7、s ascribed to the photothermal eect of Au nanocages (Figure 6B, which not only results in the shrunken state of the PNIPAM polymer shell and small hydrodynamic diameter exposing the pores of mesoporous silica for faster release, but also triggers more DOX release from the carrier by heating. It is w

8、orth noting that the DOX release is still increasing with the lower pH upon NIR irradiation. Considering that the positively charged DOX molecules are loaded in the Au-nanocagemSiO2PNIPAM nanocarriers through electrostatic interaction with the negatively charged mesoporous silica channels, which is

9、very sensitive to the acids by means of the protonation of silanols and dissociation of electrostatic interaction between DOX and silica surface at decreased pH. Furthermore, the electrostatic interaction decreases as the temperature increases; as a result, more DOX molecules are released, because o

10、f the photo3035 thermal eect of nanocarriers under the NIR irradiation. These would expect that the NIR-triggered release is also pHdependent. Such a pH-dependent release is important for cancer therapy, because of the lower pH value in tumor tissue, compared to normal tissue. To further illustrate

11、the NIR-stimulus controlled drug release, we rst examined the cytotoxicity of the DOX-loaded carrier (denoted as Carrier+DOX and free DOX. The DOX loaded in the carrier reveals lower cell viability than free DOX at various concentrations (see Figure 6C. It should be mentioned that here both free DOX

12、 and Carrier+DOX were shown to exhibit relatively low cell cytotoxicity, as a result of the short incubation time (8 h and the minor amount of DOX release from the carrier without NIR laser irradiation. Furthermore, it is observed that the uorescence signals inside the HeLa cells of free DOX are muc

13、h weaker than those for Carrier+DOX (see Figure S10 in the Supporting Information. These results show that the DOX loaded in the carrier with larger sizes can be taken up by HeLa cells through endocytosis more easily than free DOX. Similarly, only NIR laser irradiation without the carrier has a mino

14、r eect on the cell viability (see Figure 6C. We also investigated the combination of chemophotothermal therapy. For example, at a concentration of 50 g mL1, the cell viability of the DOX-loaded carrier with NIR irradiation (denoted as Carrier+DOX+Laser can be reduced to 19.9%, which is much lower th

15、an that for chemotherapy (Carrier+DOX, without NIR irradiation (85.5% and photothermal therapy (Carrier+Laser, without DOX (80.6% (see Figure 6C. The cell killing ecacy of the DOX-loaded carrier with NIR irradiation (80.1% is even much higher than the sum of chemotherapy (14.5% and photothermal ther

16、apy (19.4%, which also can be conrmed by the Trypan-blue-stained viability test (see Figure 6D. Since the photothermal conversion eciency is dependent on the ratio of adsorption to the extinction, it is also related to the SPR peak, surface property, nanocrystal volume, and so on.50 In this study, t

17、he low cell killing phenomenon of Carrier+Laser can be ascribed to the decreasing photothermal conversion eciency of Carrier after the mesoporous and polymer coating. At the other concentrations (10, 20, and 30 g mL1, the Carrier+DOX +Laser shows the highest cell killing ecacy among the sum of Carri

18、er+DOX and Carrier+Laser (Figure 6C. These results demonstrate that our Au-nanocagemSiO2PNIPAM nanocarrier can successfully achieve the eectiveness of the combination of chemotherapy and photothermal therapy and realize the synergistic eect for cancer cell killing. Moreover, the outstanding synergis

19、tic eect is ascribed to the absorption of NIR light by the nanocarrier and its subsequent conversion into heat, which not only acts as the photothermal eect to kill cells, but also results in the thermo-induced collapse of the PNIPAM polymer shell with small hydrodynamic diameter and exposes the por

20、es of mesoporous silica to trigger more DOX release from the carrier. 4. CONCLUSION In conclusion, we have developed a novel multifunctional nearinfrared (NIR-stimulus controlled drug release system based on Au-nanocagemSiO2PNIPAM coreshell nanocarrier. The unique Au-nanocagemSiO2 nanocarrier was el

21、aborately fabricated by utilizing a yolkshell Ag-nanocubemSiO2 nanostructure as a template by means of spatially conned galvanic replacement, and then the thermosensitive polymer PNIPAM shell was covalently anchored on the surface of /10.1021/cm401115b | Chem. Mater. 2013, 25, 30303037 Che

22、mistry of Materials mesoporous silica. The Au nanocage cores can eectively absorb and convert NIR light to heat upon irradiation with NIR laser. The smart PNIPAM shells as the gatekeeper can realize a thermo-induced collapse of polymer chain and expose the pores of mesoporous silica shell, thereby r

23、eleasing the preloaded drug. The in vitro studies have clearly demonstrated that the feasibility and advantage of the novel nanocarriers for remotecontrolled drug release system. More importantly, this nanocarrier can achieve the synergistic chemo-photothermal therapy eect and signicantly enhance ca

24、ncer cell killing ecacy. Such a controlled nanocarrier is expected to be widely used in biomedical applications and especially for cancer therapy. Article S ASSOCIATED CONTENT * Supporting Information Schematic procedure for the preparation of (A Ag nanocubes and (B Au-nanocagemSiO2PNIPAM nanocarrie

25、r (Figure S1. Physicochemical properties of the coreshell Ag-nanocubeSiO2mSiO2, yolkshell YS-Ag-nanocubemSiO2, and Au-nanocagemSiO2 (Table S1. UVvisible extinction spectra of (a the Ag nanocubes, (b coreshell AgnanocubeSiO2, (c Ag-nanocubeSiO2mSiO2, and (d yolk-shell Ag-nanocubemSiO2 (Figure S2. FES

26、EM images of Ag nanocubes after the spatially conned galvanic replacement reaction with dierent volumes of 0.5 mM HAuCl4 solution (Figure S3. SEM image, energy-dispersive X-ray (EDX analysis, XRD patterns, and cell viabilities of HeLa cells of the Au-nanocagemSiO2PNIPAM nanocarriers (Figures S4S7. C

27、onfocal laser scanning microscopy images of HeLa cells incubated with DOX (Figure S8A and Carrier+DOX (Figure S8B. This material is available free of charge via the Internet at . AUTHOR INFORMATION Corresponding Author *E-mail addresses: zhang_fan (F.Z., dyzhao (D.Z. These authors

28、contributed equally to this work. The authors declare no competing nancial interest. Notes ACKNOWLEDGMENTS The work was supported by the NSFC (Nos. 21101029, 21273041, 21210004, China National Key Basic Research Program (973 Project (Nos. 2013CB934101, 2013CB934104, 2012CB224805, 2010CB933901, Shang

29、hai Rising-Star Program (No. 12QA1400400, and the State Key Laboratory of Pollution Control and Resource Reuse Foundation (No. PCRRF12001. The work was also supported by the Key Subjects Innovative Talents Program of Fudan University. The author greatly acknowledges nancial support from the NPST pro

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