Anti-tumor efficacy of c(RGDfK)-decorated polypeptide-based micelles co-loaded with docetaxel and cisplatin

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• 作者：Wantong Song ; Zhaohui Tang ; Dawei Zhang ; Ying Zhang ; Haiyang Yu ; Mingqiang Li ; Shixian Lv ; Hai Sun ; Mingxiao Deng ; Xuesi Chen
• 关键词：Anti-tumor ; C(RGDfK) ; Target ; Combination ; Drug delivery
• 刊名：Biomaterials
• 出版年：March, 2014
• 年：2014
• 卷：35
• 期：9
• 页码：3005-3014
• 全文大小：3305 K

文摘

There are two important obstacles for the currently applied anti-cancer drug delivery systems. One is the conflict between long-circulation and cellular uptake while the other one is the achievement of ideal anti-cancer efficacy. To solve these problems, we designed a polypeptide-based micelle system that combined the advantages of receptor mediated endocytosis and multi-drug delivery. Firstly, an amphiphilic PLG-g-Ve/PEG graft copolymer was prepared by grafting 伪-tocopherol (Ve) and polyethylene glycol (PEG) to poly(l-glutamic acid) (PLG). Then docetaxel (DTX) and cisplatin (CDDP) were co-loaded into the PLG-g-Ve/PEG micelles via hydrophobic and chelation effect. After that, the surface of the dual-drug-loaded micelles was decorated with an 伪_v尾₃ integrin targeting peptide c(RGDfK). The targeted dual-drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In聽vivo tests demonstrated that remarkable long circulation, anti-tumor and anti-metastasis efficacy could be achieved using this drug delivery system. This work revealed a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy.