title: Design, preparation and characterization of cyclic RGDfK peptide modified poly(ethylene glycol)-block-poly(lactic acid) micelle for targeted delivery.
abstract: Molecular targeted cancer therapy is a promising strategy to overcome the lack of specificity of anticancer drug. While the binding of c(RGDfK) (cyclic Arginine-Glycine-Aspartic acid-Phenylalanine-Lysine) to αvβ3 over-expressed on tumor cell has been validated, the underlying interaction remains poorly understood. In this work, docking calculation was applied to investigate the interactions between c(RGDfK)/c(RGDfK)-PEG and αvβ3. The calculated results indicated that c(RGDfK) interacted with αvβ3 mainly by electrostatic interaction, stabilization interaction, and hydrophobic interaction. Conjugation of PEG chain to the c(RGDfK) weakened the binding affinity of c(RGDfK) to αvβ3. Accordingly, docetaxel(DTX)-loaded target micelles (c(RGDfK)-PEG-PLA/PEG-PLA/DTX) were designed, characterized and evaluated using HeLa cells. In vitro release studies demonstrated both target and non-target micelles displayed almost the same profiles, which best fit in Ritger-Peppas model. Cellular uptake and MTT studies revealed that the target micelles with the presence of c(RGDfK) were more efficiently taken up by HeLa cells and significantly improved the cytotoxicity compared to that of non-target micelles. Cell inhibition rate of target micelles was improved by 20% after 24h. Our findings suggest that target micelles may be a potential anticancer drug delivery system in the treatment of integrin αvβ3 over-expressed on tumor cell.
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China; Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810001, PR China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China.
authors.forename: Yuewei
authors.initials: Y
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China.
authors.forename: Jiexin
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Chen
authors.affiliation: School of Chemical Sciences & Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Yun
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address: leyuan@mail.buct.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Le
mesh_terms: D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003603:Cytotoxins; D008823:Micelles; D010456:Peptides, Cyclic; D011091:Polyesters; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; C033616:poly(lactide)
keywords: Docking calculations; Nano-micelle; RGDfK peptide; Target drug delivery