title: PHSCNK-Modified and doxorubicin-loaded liposomes as a dual targeting system to integrin-overexpressing tumor neovasculature and tumor cells.
abstract: The aim of this study was to prepare a liposome system targeting to both tumor angiogenesis and tumor cells, and to achieve the proof-of-principle. ATN-161 (N-acetyl-proline-histidine-serine-cysteine-asparagine-amide, PHSCN) is a ligand of integrin alpha5beta1 which is the receptor overexpressed on tumor neovasculature and some tumor cells. In this study, doxorubicin (DOX) was used as the model drug, and a derivative of PHSCN, N-acetyl-proline-histidine-serine-cysteine-asparagine-lysine (amide)-COOH (PHSCNK), was firstly coupled to the surface of PEGylated DOX liposomes (PL-DOX) by a novel approach to obtain the PHSCNK-modified and DOX-loaded PEGylated liposomes (PHSCNK-PL-DOX). These two vehicles were less than 100 nm in average, negatively charged and rather stable at 4 degrees C or 25 degrees C, while they exhibited similar release kinetics in vitro. Cell-specific uptake and cytotoxicity were investigated on human umbilical vein endothelial cells and breast cancer cells by confocal microscopy and sulforhodamine B (SRB) assay. It was found that PHSCNK-PL-DOX significantly enhanced the cell uptake and cytotoxicity of DOX on both cell lines, due to the integrin-mediated endocytosis. It was concluded that, PHSCNK-PL-DOX, which can actively delivery the drug into both tumor neovasculature and tumor cells, may be a promising targeted delivery system for anticancer drug.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Dai
authors.forename: Tingyuan
authors.initials: T
authors.lastname: Yang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008081:Liposomes; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D012235:Rhodamines / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D039081:Integrin alpha5beta1; D008081:Liposomes; D009842:Oligopeptides; D012235:Rhodamines; C022027:lissamine rhodamine B; D011092:Polyethylene Glycols; D004317:Doxorubicin