Anti-tumor efficiency of NGR-modified PEG-PLGA micelles containing paclitaxel:in vitro and in vivo  

NGR配体修饰的紫杉醇PEG-PLGA胶束抗肿瘤作用的体外体内研究(英文)

作　　者：Bing-Xiang Zhao Yue Huang Li-Min Luo Xin Zhao Xin Wang Su Chen Ke-Fu Yu Xuan Zhang Qiang Zhang 赵炳祥;黄跃;罗荔敏;赵欣;王欣;陈粟;余克富;张烜;张强(北京大学医学部天然药物及仿生药物国家重点实验室,北京100191;北京大学医学部药学院药剂学系,北京100191)

机构地区：[1]State Key Laboratories of Natural and Biomimetic Drugs,Peking University Health Science Center,Beijing 100191,China [2]Department of Pharmaceutics,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2012年第1期40-49,共10页中国药学（英文版）

基　　金：National Natural Science Foundation of China (Grant No.30873170)

摘　　要：In the present study, we prepared novel NGR-modified PEG-PLGA polymeric micelles containing paclitaxel （NGR- PM-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-tumor activity in vitro and in vivo. NGR-PM-PTX was prepared by thin-film hydration method. The in vitro targeting characteristics of NGR-modified PM on HUVEC （human umbilical vein endothelial cells）, HT1080 （human fibrosarcoma cells） and MCF-7 （human breast adenocarcinoma cells） were then investigated. The anti-tumor activity of NGR-PM-PTX was evaluated in HT1080 tumor-bearing mice in vivo. The targeting activity of the NGR-modified PM was demonstrated by flow cytometry and confocal microscopy in vitro. NGR-PM-PTX also produced marked anti-tumor activity to HTI080 tumor-beating mice in vivo.本研究制备了NGR(asparagine-glycine-arginine)配体修饰的紫杉醇PEG-PLGA胶束(NGR-PM-PTX),并对其靶向肿瘤新生血管内皮细胞及肿瘤细胞所表达的氨肽酶N进行了研究。采用薄膜法制备NGR-PM-PTX胶束。通过针对人脐静脉内皮细胞(HUVEC),人纤维肉瘤细胞(HT1080)和人乳腺癌细胞(MCF-7)的流式细胞试验和激光共聚焦实验,在体外细胞水平上研究并证实了NGR配体修饰的聚合物胶束对于上述细胞的靶向效果。HT1080荷瘤裸鼠的体内药效学研究结果进一步证实NGR-PM-PTX的抗肿瘤药效。

关 键 词：Aminopeptidase N Asn-Gly-Arg PACLITAXEL TARGETING Polymeric micelles 

分 类 号：R96[医药卫生—药理学]