A targeted nanoplatform co-delivery of pooled siRNA and doxorubicin for reversing of multidrug resistance in breast cancer
Hongmei Liu, Ding Ma, Jinpeng Chen, Ye Li, Yiping Li, Yuexia Xie, Xue Zhao, Hanbing Zou, Xiaojing Chen, Jun Pu, Peifeng Liu
Abstract
Multi-drug resistance (MDR) has become the largest obstacle to the success of cancer patients receiving traditional chemotherapeutics or novel targeted drugs. Here, we developed a targeted nanoplatform based on biodegradable boronic acid modified ε-polylysine to co-deliver P-gp siRNA, Bcl-2 siRNA, and doxorubicin for overcoming the challenge. The targeted nanoplatform showed a robust suppressing efficiency for the invasion, proliferation, and colony formation of adriamycin (ADR) resistant breast cancer cell line (MCF-7/ADR) cells in vitro. The ATP responsiveness of the nanoplatform was also proved in the research. In the in vivo antitumor experiment, the targeted nanoplatform showed a significant inhibition of tumor growth with good biocompatibility. The goal of this study is to develop a novel and facile strategy to prepare a highly efficient and safe gene and drug delivery system for MDR breast cancer based on biocompatible ε-polylysine polymers.