| Title | PHSCNK-Modified and doxorubicin-loaded liposomes as a dual targeting system to integrin-overexpressing tumor neovasculature and tumor cells. | | Author(s) | Dai W, Yang T, Wang X, Wang J, Zhang X, Zhang Q | | Institution | State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China. | | Source | J Drug Target 2009 Oct 13. | | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19824864 |
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