中国临床药学杂志

目的研究羟基喜树碱双嵌段共聚物纳米粒(MePEG-PLGA-HCPT-NPs)的抗肿瘤作用。方法选择人肝癌细胞株Bel-7402为体外模型,采用MTT法观察体外肝癌细胞的生长和增殖抑制情况,评价MePEG-PLGA-HCPT-NPs对肝癌细胞的毒性作用;采用激光共聚焦荧光显微镜技术观察其对肝癌细胞摄取药物的影响;采用小鼠H22肝癌细胞实体瘤模型进行体内抑瘤实验观察荷瘤动物的生长情况,测定肿瘤生长抑制率。结果 MePEG-PLGA-HCPT-NPs能抑制肝癌细胞的生长增殖,且随羟基喜树碱浓度的升高而增强;激光共聚焦荧光照片显示载药纳米粒能有效地被Bel-7402细胞摄取;MePEG-PLGA-HCPTNPs对小鼠的H₂₂实体瘤生长具有明显的抑制作用,低、中、高剂量组的生长抑瘤率分别为37.62%、50.31%和70.25%,与对照组相比差异均有统计学意义(P<0.05)。结论 MePEG-PLGA-HCPT-NPs具有较强的体外、体内抗肿瘤作用。与羟基喜树碱注射剂相比,MePEG-PLGA-HCPT-NPs的抑瘤率更高,且与剂量有关,并对肿瘤生长的抑制更为持久。

AIM To study the antitumor effect of hydroxy camptothecin( HCPT)-loaded amphiphilic block copolymer nanoparticles( MePEG-PLGA-HCPT-NPs). METHODS The human hepatoma cell lines Bel-7402 in vitro were selected as model,the cell growth and viability inhibited by MePEG-PLGA-HCPT-NPs were observed and the antitumor cytotoxicity was evaluated by MTT assay. Cellular uptake of HCPT was observed by Confocal fluorescence microscopy( CLSM). Hepatocellular carcinoma cell H22 was subcutaneously injected into mice and MePEGPLGA-HCPT-NPs was administered to the tumor-bearing mice. The growth of tumor was measured,and the inhibitory rate of tumor growth was calculated. RESULTS Hepatoma cell growth and viability were inhibited by MePEG-PLGA-HCPT-NPs,the inhibition was enhanced with increasing concentrations. CLSM photos indicated that MePEG-PLGA-HCPT nanoparticles enhanced the intracellular uptake of HCPT in Bel-7402 cells. Marked inhibitory effect of MePEG-PLGA-HCPT-NPs on the transplanted hepatocellular carcinoma H22 was observed in the tumorbearing mice. The inhibitory rates were 37. 62%,50. 31% and 70. 25% in the groups treated with low,medium and high dosage of MePEG-PLGA-HCPT-NPs,respectively( P < 0. 05 vs control group). CONCLUSION MePEG-PLGA-HCPT-NPs has marked inhibitory effects on tumor growth in vitro and in vivo. The inhibitory effect of MePEG-PLGA-HCPT-NPs is obvious and dose-dependent and higher than that of HCPT injection.