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, The CIAC researchers 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 a-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-drugloaded micelles was decorated with an avb3 integrin targeting peptide c(RGDfK). The targeted dual drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In vivo tests demonstrated that remarkable long circulation, anti-tumor and antimetastasis efficacy could be achieved using this drug delivery system. This work is believed to reveal a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy.
The research results have been published in Biomaterials 35 (2014) 3005-3014.
2009-2016 Changchun Institute Of Applied Chemistry, Chinese Academy Of Sciences, All