李 翔, 张 婧, 王东凯, 潘卫三. 叶酸受体靶向多烯紫杉醇膜修饰脂质体的抗肿瘤活性J. 药学学报, 2013,48(7): 1142-1147.
引用本文: 李 翔, 张 婧, 王东凯, 潘卫三. 叶酸受体靶向多烯紫杉醇膜修饰脂质体的抗肿瘤活性J. 药学学报, 2013,48(7): 1142-1147.
LI Xiang, ZHANG Jing, WANG Dong-kai, PAN Wei-san. Anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomesJ. 药学学报, 2013,48(7): 1142-1147.
Citation: LI Xiang, ZHANG Jing, WANG Dong-kai, PAN Wei-san. Anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomesJ. 药学学报, 2013,48(7): 1142-1147.

叶酸受体靶向多烯紫杉醇膜修饰脂质体的抗肿瘤活性

Anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes

  • 摘要:

    研究叶酸受体靶向多烯紫杉醇膜修饰脂质体 (FA-PDCT-L) 的体内外抗肿瘤活性。采用有机溶剂注入法制备FA-PDCT-L并利用透射电镜、粒径zeta电位测定仪考察其理化性质。采用CCK-8法检测多烯紫杉醇注射液 (DCT-I)、未修饰DCT脂质体 (DCT-L) FA-PDCT-L在不同孵育时间对MCF-7A549肿瘤细胞的生长抑制作用, 并进行体外溶血性实验; 将荷瘤小鼠随机分为DCT-IDCT-LFA-PDCT-L和对照组 (生理盐水),  10 mg·kg−1·d−1尾静脉注射给药, 实验结束后测定各组小鼠体重、瘤重, 并计算抑瘤率, 进行生存分析。结果显示: FA-PDCT-LMCF-7A549IC50值在各时间点均显著低于DCT-I组及DCT-L, 且在体外4 h未见溶血现象。与对照组相比, DCT-IDCT-LFA-PDCT-L组小鼠瘤重均减少, 其中FA-PDCT-L的作用最为显著, 抑瘤率为79.03 % (P < 0.05); FA-PDCT-L生存曲线和中位生存时间显著高于DCT-IDCT-L。该研究表明FA-PDCT-L具有良好的抗癌活性, 有望成为肿瘤治疗中DCT的优良载体。

     

    Abstract:

    The anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes (FA-PDCT-L) was investigated in vitro and in vivo.  FA-PDCT-L was prepared by organic solvent injection method.  Transmission electron microscope, dynamic light scattering and electrophoretic light scattering were employed to study the physicochemical parameters of FA-PDCT-L.  The inhibitory effects of docetaxel injection (DCT-I), non-modified DCT liposomes (DCT-L) and FA-PDCT-L on the growth of MCF-7 and A-549 cells at different incubation times were detected by CCK-8 assay; and the hemolytic test was employed in vitro.  Tumor mice were randomized into 4 groups: DCT-I, DCT-L, FA-PDCT-L and control group (normal saline), and given drugs at 10 mg·kg−1·d−1 through tail vein.  The tumor volume, mice weight, inhibition rate of tumor and life span were measured at the end of experiments.  The IC50 of the FA-PDCT-L for MCF-7 and A549 cell lines were significantly lower than that of DCT-I and DCT-L, without hemolysis reaction observed.  Compared with control group, the weights of tumor in DCT-I, DCT-L and FA-PDCT-L were decreased, especially for FA-PDCT-L, with inhibitory rates at 79.03 % (P < 0.05).  The life span and median survival time of FA-PDCT-L treated mice were significantly higher than that of DCT-I and DCT-L.  In conclusion, FA-PDCT-L shows a good anti-tumor activity, indicating that it is potential carriers for DCT in the treatment of tumor.

     

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