目的研究新型的乳糖化-去甲斑蝥素纳米粒(Lac-NCTD-NPs)的体内外抗癌活性。方法通过MTT法考察去甲斑蝥素(NCTD)、乳糖化-去甲斑蝥素(Lac-NCTD)及Lac-NCTD-NPs对肿瘤细胞株HepG2、SMMC-7721和SGC-7901的细胞毒作用和半乳糖化小牛血清(Gal-FBS)的竞争性抑制作用;采用HPLC法评价肝肿瘤细胞SMMC-7721对Lac-NCTD的摄取效果;通过H22荷瘤小鼠模型考察药物体内对肝癌的抑制作用。结果 体外细胞毒试验结果显示,对HepG2和SMMC-7721细胞,培养48 h时Lac-NCTD-NPs的IC50最低,细胞毒作用最强,其次是Lac-NCTD,且均能显著地被Gal-FBS抑制;对SGC-7901细胞,Lac-NCTD-NPs和Lac-NCTD的细胞毒作用并不比NCTD强,且不受Gal-FBS的影响;培养12 h后SMMC-7721对Lac-NCTD的摄取量为3.89μg(7.02×10^-3μmol,1×10⁶个细胞);小鼠体内抑瘤实验结果显示Lac-NCTD-NPs中剂量的抑瘤率为63.9%,显著高于相同浓度的NCTD和Lac-NCTD。结论 Lac-NCTD-NPs能有效地靶向于肝肿瘤组织,抑制肿瘤的生长,是一种强的具有体内外抗癌活性的新型肝靶向性制剂。

Objective To investigate the anticancer activity of the novel lactosyl-norcantharidin nano-particles(Lac-NCTD-NPs) in vivo and in vitro.Methods The MTT method was used to study the cytotoxic effects of Lac-NCTD and Lac-NCTD-NPs on HepG2,SMMC-7721,and SGC-7901 cell lines for 12 and 48 h,respectively,and the inhibitory effects of Gal-FBS;Lac-NCTD accumulated in SMMC-7721 cells was assayed by HPLC;The in vivo anticancer activity was evaluated by the tumor-growth inhibition in H22 tumor bearing mice.Results The in vitro studies showed that the cytotoxic effects of Lac-NCTD-NPs against HepG2 and SMMC-7721 cells were the most powerful,as well as the IC50 was the lowest,then Lac-NCTD,and they were inhibited remarkably by Gal-FBS;As for SGC-7901 cell line,the cytotoxic effects of Lac-NCTD-NPs and Lac-NCTD were not stronger than that of NCTD,and Gal-FBS had no influence on them at all;The amount of Lac-NCTD accumulated in SMMC-7721 cells was 3.89 μg(7.02×10^-3 μmol,1×10⁶ cell) after treatment for 12 h;The results of the antitumor activity in vivo suggested that the inhibitory rate of Lac-NCTD-NPs on tumor weight was 63.9%,which was significantly higher than that of NCTD and Lac-NCTD groups at the same molar concentration.Conclusion The tumor-growth is inhibited effectively by Lac-NCTD-NPs which may be a kind of novel liver-targeting agents and could strongly inhibit the tumor-growth.

国家科技支撑计划课题资助项目(2006BAI09B00);国家科技部科技型中小企业技术创新基金项目(07C26223201333);江苏省“六大人才高峰”资助项目;江苏省卫生厅招标项目(H200630)