Block copolymer@ZIF-8 nanocomposites as a pH-responsive multi-steps release system for controlled drug delivery
Zhentao Lei, Qiuju Tang, Yanshan Ju, Yonghui Lin, Xiaowen Bai, Haipeng Luo, Zaizai Tong
Abstract
Developing the hybrid nanosystems for controlled drug release is still a challenging task. In this work, pH-responsive core-shell nanocomposites have been prepared by the growth of zeolitic imidazolate framework-8 (ZIF-8) on the surface of polymeric aggregates self-assembled from poly(ε-caprolactone)-block-poly (quaternized vinylbenzyl chloride/bipyridine) (PCL-b-q(PVBC/BPy), BCP for short) in water. The core of the micelles or the inner cavity of vesicles serves as the drug storage reservoir for the doxorubicin hydrochloride (DOX) and the ZIF-8 shells act as the gatekeepers to prevent drug premature release at physiological environment. Upon pH stimulus, the core-shell nanocomposites (BCP@ZIF-8) show a retarded drug release behavior compared with DOX-loaded polymeric aggregates counterparts (without the shell of ZIF-8). Moreover, the as-prepared nanocomposites perform good biocompatibility towards MCF-7 cell. Meanwhile, the DOX-loaded BCP@ZIF-8 nanocomposites present lower cytotoxicity compared with DOX-loaded BCP and free DOX. The confocal microscopy study shows the core-shell nanocomposites could be efficiently internalized by cancer cells, and the loaded DOX could be successfully released under acidic intracellular environment. The above result shows that the core-shell nanocomposite could be a promising candidate for pH-responsive drug delivery system in the cancer therapy.