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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 study the anticancer activity of a novel lactose-norcantharidin nanoparticles (Lac-NCTD-NPs) in vitro and in vivo. Methods The cytotoxicity of NCTD, Lac-NCTD and Lac-NCTD-NPs on HepG2, SMMC-7721 and SGC-7901 cells were studied by MTT assay. The inhibitory effect of Gal-FBS was evaluated by HPLC. The uptake of Lac-NCTD by hepatic tumor cell SMMC-7721 was evaluated by HPLC. The inhibitory effect of the drug on hepatocarcinoma was evaluated by H22 tumor-bearing mouse model. Results The results of in vitro cytotoxicity assay showed that Lac-NCTD-NPs had the lowest IC50 and the highest cytotoxicity, followed by Lac-NCTD for 48 h in HepG2 and SMMC-7721 cells, and all of them were significantly inhibited by Gal-FBS The cytotoxicity of Lac-NCTD-NPs and Lac-NCTD in SGC-7901 cells was not stronger than that in NCTD, and was not affected by Gal-FBS. The uptake of Lac-NCTD by SMMC-7721 after cultured for 12 h was 3.89μg (7.02 × 10-3μmol, 1 × 106cells). The antitumor activity in mice showed that the inhibition rate of Lac-NCTD-NPs was 63.9%, which was significantly higher than that of NCTD and Lac-NCTD . Conclusions Lac-NCTD-NPs can effectively target the liver tumor tissue and inhibit the growth of the tumor. It is a novel hepatotropic agent with anticancer activity in vivo and in vitro.