title: Anti-tumor efficacy of c(RGDfK)-decorated polypeptide-based micelles co-loaded with docetaxel and cisplatin.
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 αvβ3 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.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Wantong
authors.initials: W
authors.lastname: Song
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: ztang@ciac.ac.cn.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yu
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China.
authors.forename: Shixian
authors.initials: S
authors.lastname: Lv
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130021, PR China.
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Deng
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000077143:Docetaxel; D004705:Endocytosis / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D057446:Hydrodynamics; D009682:Magnetic Resonance Spectroscopy; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011099:Polyglutamic Acid / Q000138:chemical synthesis / Q000737:chemistry; D043823:Taxoids / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D014018:Tissue Distribution / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D010455:Peptides; D043823:Taxoids; D000077143:Docetaxel; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D002945:Cisplatin
keywords: Anti-tumor; C(RGDfK); Combination; Drug delivery; Target