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NGR-modified micelles enhance their interaction with CD13-overexpressing tumor and endothelial cells
Wang, Xun; Wang, Yiguang; Chen, Xiaomei; Wang, Jiancheng; Zhang, Xuan; Zhang, Qiang
关键词NGR CD13 Docetaxel Polymeric micelles CD13-overexpressing tumor
刊名JOURNAL OF CONTROLLED RELEASE
2009-10-01
DOI10.1016/j.jconrel.2009.05.030
139期:1页:56-62
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]AMINOPEPTIDASE-N ; POLYMERIC MICELLES ; DRUG-DELIVERY ; PEPTIDES ; CHEMOTHERAPY ; DOCETAXEL ; BINDING ; CANCER ; FORMULATION ; PACLITAXEL
英文摘要

Certain tumor cells and most tumor endothelial cells overexpress a membrane-spanning molecule, aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the Asn-Gly-Arg (NGR) motif. NGR-modified docetaxel (DTX)-loaded PEG-b-PLA polymeric micelles (NGR-PM-DTX) were firstly developed and tested in vitro and in vivo, while DTX-loaded polymeric micelles (PM-DTX) and free DTX were used as controls. The NGR-PM-DTX containing DTX were about 35 nm in diameter with spherical shape and high encapsulation efficiency. It was demonstrated quantitatively by the spectrophotofluorometry and qualitatively by the confocal image analysis that NGR facilitates the uptake of micelles by CD13-overexpressed tumor cells (fibrosarcoma, HT1080) and endothelial cells (human umbilical vein endothelial cells. HUVEC). Free NGR inhibited cellular uptake of NGR-PM-DTX, revealing the mechanism of receptor-mediated endocytosis. Higher cytotoxicity, toward HT1080 cells and more efficient inhibition of HUVEC proliferation were also observed in NGR-PM-DTX groups, which were consistent well with the observation of cellular uptake. In BALB/c mice bearing HT1080 tumor xenografts, stronger antitumor efficacy and less body weight changes were shown in NGR-PM-DTX group, with good correlation between in vitro and in vivo. Therefore, it was concluded that NGR-PM could be a potential vehicle for delivering hydrophobic chemotherapeutic agents to CD13-overexpressing tumors. (C) 2009 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000270115800009
项目编号2009CB930300 ; 2007AA021811
资助机构National Basic Research Program of China ; 863 Project
引用统计
被引频次:59[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62396
专题北京大学药学院
北京大学药学院_药剂学系
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
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GB/T 7714
Wang, Xun,Wang, Yiguang,Chen, Xiaomei,et al. NGR-modified micelles enhance their interaction with CD13-overexpressing tumor and endothelial cells[J]. JOURNAL OF CONTROLLED RELEASE,2009,139(1):56-62.
APA Wang, Xun,Wang, Yiguang,Chen, Xiaomei,Wang, Jiancheng,Zhang, Xuan,&Zhang, Qiang.(2009).NGR-modified micelles enhance their interaction with CD13-overexpressing tumor and endothelial cells.JOURNAL OF CONTROLLED RELEASE,139(1),56-62.
MLA Wang, Xun,et al."NGR-modified micelles enhance their interaction with CD13-overexpressing tumor and endothelial cells".JOURNAL OF CONTROLLED RELEASE 139.1(2009):56-62.
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