Anti-tumor and anti-angiogenic effect of metronomic cyclic NGR-modified liposomes containing paclitaxel

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• 作者：Li-Min Luo^a ; ¹ ; Yue Huang^a ; ¹ ; Bing-Xiang Zhao^a ; Xin Zhao^a ; Yu Duan^a ; Ruo Du^a ; Ke-Fu Yu^a ; Ping Song^a ; Yang Zhao^a ; Xuan Zhang^a ; ^{xuanzhang@bjmu.edu.cn} ; Qiang Zhang^a ; ^b
• 关键词：Aminopeptidase N (APN) ; Cyclic Asn-Gly-Arg (NGR) ; Paclitaxel (PTX) ; Targeting ; Anti-angiogenic efficacy ; Metronomic administration
• 刊名：Biomaterials
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：34
• 期：4
• 页码：1102-1114
• 全文大小：3195 K

文摘

In the present study, we prepared NGR-modified sterically stabilized liposomes containing paclitaxel (NGR-SSL-PTX) in order to evaluate their potential targeting to aminopeptidase N receptors expressed on tumor endothelial cells and the tumor cell surface and its anti-angiogenic activity following metronomic administration. NGR-SSL-PTX was prepared by a thin-film hydration method. The in?vitro targeting characteristics of NGR-modified liposomes on HUVEC (human umbilical vein endothelial cells), HT1080 (human ?brosarcoma cells) and MCF-7 (human breast adenocarcinoma cells) were then investigated. The effect of NGR-SSL-PTX on HUVEC proliferation and migration was also tested. The pharmacokinetics of NGR-SSL-PTX was studied in rats. The in?vivo targeting activity of NGR-modified liposomes was investigated in HT1080 tumor-bearing mice. The anti-tumor activity of NGR-SSL-PTX following metronomic administration was evaluated in HT1080 tumor-bearing mice in?vivo. The targeting activity of the NGR-modified liposomes was demonstrated by in?vitro flow cytometry and confocal microscopy as well as in?vivo confocal immunofluorescence microscopy and bio-distribution experiments. The results of endothelial cell proliferation and migration and microvessel density (MVD) confirmed the anti-angiogenic activity of NGR-SSL-PTX in?vitro and in?vivo. The sustained circulation of NGR-SSL-PTX was shown in the pharmacokinetic study. NGR-SSL-PTX is able to improve treatment efficacy producing the most significant anti-tumor activity and anti-angiogenic following metronomic administration.