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

doi:10.5246/jcps.2012.01.005

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

赵炳祥, 黄跃, 罗荔敏, 赵欣, 王欣, 陈粟, 余克富, 张烜^*, 张强

1. 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
2. 北京大学医学部药学院药剂学系, 北京 100191

收稿日期:2011-08-07 修回日期:2011-11-01 出版日期:2012-01-01 发布日期:2012-01-01
通讯作者: 张烜*

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

Bing-Xiang Zhao, Yue Huang, Li-Min Luo, Xin Zhao, Xin Wang, Su Chen, Ke-Fu Yu, Xuan Zhang^*, Qiang Zhang

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

Received:2011-08-07 Revised:2011-11-01 Online:2012-01-01 Published:2012-01-01
Contact: Xuan Zhang*

摘要/Abstract

摘要： 本研究制备了NGR (asparagineglycinearginine)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: 氨肽酶N, NGR, 紫杉醇, 靶向, 聚合物胶束

Abstract: 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 HT1080 tumor-bearing mice in vivo.

Key words: Aminopeptidase N, Asn-Gly-Arg, Paclitaxel, Targeting, Polymeric micelles

中图分类号:

R945

Supporting: Foundation item: National Natural Science Foundation of China (Grant No. 30873170).
^*Corresponding author. Tel./Fax: 86-10-82802683

赵炳祥, 黄跃, 罗荔敏, 赵欣, 王欣, 陈粟, 余克富, 张烜^*, 张强. 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[J]. , DOI: 10.5246/jcps.2012.01.005.

Bing-Xiang Zhao, Yue Huang, Li-Min Luo, Xin Zhao, Xin Wang, Su Chen, Ke-Fu Yu, Xuan Zhang^*, Qiang Zhang . Anti-tumor efficiency of NGR-modified PEG-PLGA micelles containing paclitaxel: in vitro and in vivo [J]. , DOI: 10.5246/jcps.2012.01.005.

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