摘要
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。
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.
作者
赵炳祥
黄跃
罗荔敏
赵欣
王欣
陈粟
余克富
张烜
张强
Bing-Xiang Zhao;Yue Huang;Li-Min Luo;Xin Zhao;Xin Wang;Su Chen;Ke-Fu Yu;Xuan Zhang;Qiang Zhang(State Key Laboratories of Natural and Biomimetic Drugs,Peking University Health Science Center,Beijing 100191,China;Department of Pharmaceutics,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China)
基金
National Natural Science Foundation of China (Grant No.30873170)
关键词
氨肽酶N
NGR
紫杉醇
靶向
聚合物胶束
Aminopeptidase N
Asn-Gly-Arg
Paclitaxel
Targeting
Polymeric micelles