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

• Published in: Biomaterials Vol. 35; no. 9; pp. 3005 - 3014
• Main Authors: Song, Wantong, Tang, Zhaohui, Zhang, Dawei, Zhang, Ying, Yu, Haiyang, Li, Mingqiang, Lv, Shixian, Sun, Hai, Deng, Mingxiao, Chen, Xuesi
• Format: Journal Article
• Language: English
• Published: Netherlands 01.03.2014
• Subjects: Advanced Basic Science; Amino Acid Sequence; Animals; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cell Survival - drug effects; Cisplatin - pharmacokinetics; Cisplatin - pharmacology; Cisplatin - therapeutic use; Dentistry; Endocytosis - drug effects; HeLa Cells; Humans; Hydrodynamics; Magnetic Resonance Spectroscopy; Melanoma, Experimental - drug therapy; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Micelles; Molecular Sequence Data; Neoplasm Metastasis; Peptides - chemistry; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polyglutamic Acid - chemical synthesis; Polyglutamic Acid - chemistry; Taxoids - pharmacokinetics; Taxoids - pharmacology; Taxoids - therapeutic use; Tissue Distribution - drug effects; Tumor Burden - drug effects; Target; Drug delivery; Anti-tumor; C(RGDfK); Combination
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.12.018

Abstract 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 α-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 αv β3 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 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.