【摘要】 目的研究载131I和阿霉素“双弹头”F(ab′)2片段免疫毫微粒的抗肿瘤效应及其在荷瘤裸鼠体内的分布。方法采用氯胺T法,将核素131I结合到抗人肝癌HAb18抗体的F(ab′)2片段靶向的载阿霉素毫微粒上,构建“双弹头”F(ab′)2片段免疫毫微粒;采用花环形成实验、MTT比色分析法等分别研究该免疫毫微粒对人肝癌细胞株(SMMC-7721)的特异性结合及体外细胞毒作用;应用皮下荷人肝癌裸鼠模型,评价该免疫毫微粒的体内分布及其抗肝癌作用。结果“双弹头”F(ab′)2片段免疫毫微粒能特异性结合于SMMC-7721细胞周围形成花环,其IC50明显低于“单弹头”F(ab′)2片段免疫毫微粒;该免疫毫微粒经尾静脉给药后,主要分布于肝、脾等处,而经瘤体注射主要滞留于瘤体内,其抑瘤率显著高于对照“单弹头”毫微粒。结论载131I和阿霉素“双弹头”F(ab′)2片段免疫毫微粒,具有较“单弹头”F(ab′)2片段免疫毫微粒更佳的抗肿瘤效应。更多还原

【Abstract】 Objective To study anti-tumour actitivities and in vivo distributions of F（ab′）₂ fragment-targeted “two bullet” immunonanoparticles.Methods For constructing F（ab′）₂ fragment-targeted “two bullet” immunonanoparticles,ammonia chroloric T technique was used for coupling radioisotope ¹³¹I to adrimycin-loaded human serum albumin immunonanoparticles directed by F（ab′）₂ fragment of anti-human hepatoma antibody HAb18; Rosset forming test and MTT colorimetric assay were used respectively to assay specific binding or in vitro cytotoxicities of the “two bullet” immunonanoparticles to human hepatoma cell line SMCC-7721; The hepatoma-bearing nude mice were used for analyzing in vivo distributions and antitumor effects of the “two bullet” immunonanoparticles.Results The “two bullet” immunonanoparticles could bind specifically to surface of SMMC-7721 cells and exhibit stronger in vitro cytotoxicities on SMMC-7721 cells than “single bullet” immunonanoparticles,with IC 50 of 17.13 μg/ml vs 73.5 μg/ml.They mainly concentrated in liver,spleen,etc after being administered intravenously and remained in tumor for much longer time after being administered intratumorously,which had higher inhibitory rate of tumor than “single bullet” immunonanoparticle controls.Conclusion F（ab′）₂ fragment-targeted “two bullet” immunonanoparticles could exhibit much better anti-tumor effects than F（ab′）₂ fragment-targeted “single bullet” immunonanoparticles.更多还原