上海交通大学学报(医学版)

• 论著(基础研究) • 上一篇    下一篇

载多烯紫杉醇的转铁蛋白修饰脂质体的制备及其体外抗脑胶质瘤的作用

缪伟锋,吴一平,喻永涛,姚建社,羊正祥   

  1. 无锡市人民医院神经外科, 无锡 214023
  • 出版日期:2013-12-28 发布日期:2014-01-02
  • 作者简介:缪伟锋(1977—), 男, 主治医师, 学士; 电子信箱: wxmwf@126.com。

Preparation of docetaxel loaded transferrin modified liposome and its in vitro anti-glioma effect

MIAO Wei-feng, WU Yi-ping, YU Yong-tao, YAO Jian-she, YANG Zheng-xiang   

  1. Department of Neurosurgery, Wuxi People's Hospital, Wuxi 214023, China
  • Online:2013-12-28 Published:2014-01-02

摘要:

目的 以鼠脑胶质瘤细胞C6和鼠脑内皮细胞bEnd.3为模型,研究载多烯紫杉醇(DOC)的转铁蛋白(TF)修饰脂质体(DOC-TF-LP)的体外抗肿瘤作用。方法 采用薄膜分散法制备普通脂质体(LP),后插入法制备TF修饰LP(TF-LP)。荧光定量实验观察C6细胞和bEnd.3细胞对TF-LP和LP的摄取。MTT实验检测不同LP对肿瘤细胞的增殖抑制作用。构建C6细胞肿瘤球模型,观察不同LP对肿瘤球的穿透能力以及对肿瘤球体积的增长抑制能力。结果 脑胶质瘤C6细胞对TF-LP的摄取效率是LP的3.2倍(P<0.05);脑内皮细胞bEnd.3对TF-LP的摄取效率是LP的2.6倍(P<0.05)。DOC-TF-LP对肿瘤细胞的增殖抑制作用显著大于DOC-LP和DOC游离溶液(P<0.05)。载香豆素-6的TF-LP与肿瘤球共孵育4 h后,TF-LP的荧光强度强于LP。DOC游离溶液、DOC-LP和DOC-TF-LP分别使肿瘤体积减小到原体积的80%、65%和38%。结论 与DOC和DOC-LP相比,DOC-TF-LP能够更加有效地被脑内皮细胞和肿瘤细胞摄取,抑制肿瘤细胞增殖及肿瘤球生长,具有更强的抗肿瘤作用。

关键词: 转铁蛋白, 多烯紫杉醇, 脂质体, 脑胶质瘤

Abstract:

Objective To determine the anti-tumor effect of the novel docetaxel (DOC) loaded transferrin modified liposome (DOC-TF-LP) on rat glioma cell line C6. Methods LP
was prepared by film-ultrasonic method. Cellular uptake by brain capillary endothelial cells (bEnd.3) and C6 glioma cells was observed by fluorescence quantitative experiment. The anti-proliferation efficiency of DOC-TF-LP was evaluated by MTT assay. Tumor spheroids were used to evaluate the targeting efficiency and anti-tumor ability of DOC-TF-LP. Results Efficiency of TF-LP cellular uptake by C6 glioma cells was 3.2 times of LP (P<0.05). Efficiency of TF-LP cellular uptake by bEnd.3 was 2.6 times of LP (P<0.05). The anti-proliferative activity of DOC-TF-LP were higher than those of DOC-LP and DOC (P<0.05). Fluorescence intensity of TF-LP was higher than that of LP after incubation with C6 tumor spheroids. Gross tumor volumes decreased to 80%, 65%, and 38% after incubation with DOC, DOC-LP, and DOC-TF-LP, respectively. Conclusion Compared to DOC and DOC-LP, DOC-TF-LP could more persistently inhibit the proliferation of C6 cells and C6 tumor spheroids. Thus, DOC-TF-LP, as a new nanometer drug, has a special application value for the therapy of glioma.

Key words: transferrin, docetaxel, liposome, glioma