Amphiphilic prodrug-decorated graphene oxide as a multi-functional drug delivery system for efficient cancer therapy

作者:Huang, Chunzhi; Wu, Jilian; Jiang, Wei; Liu, Ruiling; Li, Zhonghao; Luan, Yuxia*
来源:Materials Science & Engineering C-Materials for Biological Applications, 2018, 89: 15-24.
DOI:10.1016/j.msec.2018.03.017

摘要

Graphene oxide (GO) has shown great potential in drug delivery. However, the aqueous stability, non-specific drug release and slow release rate are major problems of the GO-based drug delivery system. Herein, we for the first time integrate the dispersant, stabilizing agent and active targeting carrier into a novel drug delivery system based on GO/PP-SS-DOX nanohybrids. The redox-sensitive PP-SS-DOX prodrug was obtained by conjugating mPEG-PLGA (PP) with doxorubicin (DOX) via disulfide bond. PEG-FA provided active targeting property for the constructed drug delivery system, GO/PP-SS-DOX/PEG-FA. In this demonstrated system, PP-SS-DOX markedly increases the stability in physiological solutions of GO and guarantees the DOX release in the reductive environment (cancerous cells). And PEG-FA helps target to cancerous tissues and induces FR-mediated endocytosis. In vitro drug release exhibited the obvious reductive sensitivity and the cumulative release amount was up to 90%, while 40% in previous reports within 72 h. The in vitro cytotoxicity of targeting nanohybrids was significantly cytotoxic than that of non-targeting nanohybrids. In vivo results displayed that the as-prepared targeting nanohybrids showed efficacious antitumor effect while it had nearly no systemic adverse toxicity on B16 tumor-bearing mice. Therefore, the in vitro and in vivo results indicate that our constructed GO/PP-SS-DOX/PEG-FA drug delivery system is a promising carrier in cancer therapy.