Nanoscale Metal–Organic-Frameworks Coated by Biodegradable Organosilica for pH and Redox Dual Responsive Drug Release and High-Performance Anticancer Therapy

• DOI: 10.1021/acsami.9b04236
• Publication Date: 2019-05-13T10:42:38Z
• Authors: Shen-Zhen Ren; Dan Zhu; Xiao-Hua Zhu; Bin Wang; Yu-Shun Yang; Wen-Xue Sun; Xiao-Ming Wang; Peng-Cheng Lv; Zhong-Chang Wang; Hai-Liang Zhu
• Keywords: Mice, Inbred BALB C; Apoptosis; Hydrogen-Ion Concentration; Flow Cytometry; Silicon Dioxide; 01 natural sciences; 0104 chemical sciences; 3. Good health; Drug Liberation; Mice; Drug Delivery Systems; Microscopy, Electron, Transmission; Doxorubicin; Spectroscopy, Fourier Transform Infrared; MCF-7 Cells; Animals; Humans; Nanoparticles; Female; Reactive Oxygen Species; Oxidation-Reduction; Metal-Organic Frameworks; HeLa Cells

Responsive nanocarriers with biocompatibility and precise drug releasing capability have emerged as a prospective candidate for anticancer treatment. However, the challenges imposed by the complicated preparation process and limited loading capacities have seriously impeded the development of novel multifunctional drug delivery systems. Here, we developed a novel and dual-responsive nanocarrier based on a nanoscale ZIF-8 core and an organosilica shell containing disulfide bridges in its frameworks through a facile and efficient strategy. The prepared ZIF-8@DOX@organosilica nanoparticles (ZDOS NPs) exhibited a well-defined structure and excellent doxorubicin (DOX) loading capability (41.2%) with pH and redox dual-sensitive release properties. The degradation of the organosilica shell was observed after 12 h incubation with a 10 mM reducing agent. Confocal imaging and flow cytometry analysis further proved that the nanocarriers can efficiently enter cells and complete intracellular DOX release under the low pH and high glutathione concentrations, which resulted in an enhanced cytotoxicity of DOX for cancer cells. Meanwhile, subcellular localization experiments revealed that the ZDOS NPs entered cells mainly by endocytosis and then escaped from lysosomes into the cytosol. Moreover, in vivo assays also demonstrated that the ZDOS NPs exhibited negligible systemic toxicity and significantly enhanced anticancer efficiencies compared with free DOX. In summary, our prepared pH and redox dual-responsive nanocarriers provide a potential platform for controlled release and cancer treatment.