ZnO–DOX@ZIF-8 Core–Shell Nanoparticles for pH-Responsive Drug Delivery

Developing multifunctional hybrid nanosystems for controlled drug delivery is a challenging task. In this work, we prepared hierarchical core–shell nanoparticles (ZnO–DOX@ZIF-8) composed of mesoporous ZnO core and microporous ZIF-8 shell, in which the core serves as the drug storage reservoir for the loading of anticancer drug doxorubicin (DOX) and the shell could be used to prevent premature release of loaded drug at physiological environment. The mesoporous ZnO nanoparticles were first prepared, followed by DOX drug loading. Such ZnO nanoparticles were then employed as the zinc source to react with 2-methylimidazole for the formation of ZnO–DOX@ZIF-8 core–shell nanoparticles. The core–shell nanoparticles exhibit good dispersibility and stability as well as pH-responsive drug release property. While only up to 20% of loaded DOX was released in the buffer of pH 7.4, over 80% of DOX was released in the buffer of pH 5.5 because of the decomposition of the ZIF-8 shell as well as the dissolution of the ZnO core under acidic conditions. The confocal microscopy studies show that the core–shell nanoparticles could be efficiently internalized by cancer cells, and the loaded DOX in the nanoparticles could be successfully released under acidic intracellular environment. The in vitro cytotoxicity measurements demonstrate that the core–shell nanoparticles free of drug exhibit a significant cytotoxicity when the concentration was above 25 μg/mL on account of the production of reactive oxygen species. The reactive oxygen species are only generated in acidic condition, which could combine with DOX for a synergistic cancer treatment with satisfactory therapeutic efficacy. On the other hand, the nanoparticles were stable and nontoxic in physiological environment. Thus, the ZnO–DOX@ZIF-8 core–shell nanoparticles are a promising pH-responsive drug delivery system for the cancer therapy.