title: A synthetic peptide mediated active targeting of cisplatin liposomes to Tie2 expressing cells.
abstract: Tie2 receptor is a receptor tyrosine kinase that plays important roles in vascular angiogenesis, and also highly expressed by a number of cancer cells. In this study, we reported an active targeting liposome system directed by a novel peptide ligand PH1 that can improve drug efficacies specifically to Tie2 expressing cells. The PH1 peptide (TMGFTAPRFPHY) was selected by phage display library screening combined with surface plasmon resonance binding assays. It was covalently conjugated to the distal end of DSPE-PEG(2000)-Maleimide lipid and loaded onto liposome membranes as the targeting ligand. These PH1-PEG-liposomes containing the anticancer drug cisplatin were showed to bind tightly to Tie2 positive cells, mediate active endocytosis of the drug containing liposomes, and result in much higher cell specific cytoxicities than mPEG coated liposomes. They can be used not only to target vascular endothelial cells for anti-angiogenesis effects, but also to improve drug delivery and release in Tie2 expressing cancer cells. Such liposome formulation may be developed into a very useful agent for metronomic chemotherapy.
authors: School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, PR China.
authors: Junhua
authors: J
authors: Mai
authors: Shuxian
authors: S
authors: Song
authors: Mengjie
authors: M
authors: Rui
authors: Dan
authors: D
authors: Liu
authors: Qian
authors: Q
authors: Ding
authors: Jinliang
authors: J
authors: Peng
authors: Yuhong
authors: Y
authors: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008081:Liposomes; D008301:Maleimides / Q000737:chemistry; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D019151:Peptide Library; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D013997:Time Factors
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D008301:Maleimides; D009842:Oligopeptides; D019151:Peptide Library; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D042787:Receptor, TIE-2; D002945:Cisplatin