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学科主题: 药学
题名:
PHSCNK-Modified and doxorubicin-loaded liposomes as a dual targeting system to integrin-overexpressing tumor neovasculature and tumor cells
作者: Dai, Wenbing; Yang, Tingyuan; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Zhang, Qiang
关键词: Dual targeting system ; liposomes ; doxorubicin ; PHSCNK ; integrins ; neovasculature ; tumor cells
刊名: JOURNAL OF DRUG TARGETING
发表日期: 2010-05-01
DOI: 10.3109/10611860903353354
卷: 18, 期:4, 页:254-263
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: STERICALLY STABILIZED LIPOSOMES ; IMPROVED ANTITUMOR EFFICACY ; IN-VIVO ; INTRACELLULAR DELIVERY ; CANCER-CELLS ; RGD PEPTIDE ; ANGIOGENESIS ; VITRO ; IMMUNOLIPOSOMES ; TRANSFERRIN
英文摘要:

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 alpha 5 beta 1 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.

语种: 英语
所属项目编号: 2009CB930300 ; 2007CB935901 ; 2007AA021811
项目资助者: National Basic Research Program of China ; 863 Project
WOS记录号: WOS:000276623600002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59270
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Dai, Wenbing,Yang, Tingyuan,Wang, Xueqing,et al. PHSCNK-Modified and doxorubicin-loaded liposomes as a dual targeting system to integrin-overexpressing tumor neovasculature and tumor cells[J]. JOURNAL OF DRUG TARGETING,2010,18(4):254-263.
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