抗人肝癌免疫毫微球的制备及其抗癌效果观察  

Antitumor effect of nanospheres coupled with the anti-human liver cancer monoclonal antibody HAb18

作　　者：阚和平[1] 刘正军[1] 谭永法[1] 林艺雄[1] 李春芳[1] 周杰[1] 

机构地区：[1]南方医科大学南方医院肝胆外科,广东广州510515

出　　处：《南方医科大学学报》2008年第8期1503-1505,共3页Journal of Southern Medical University

基　　金：广东省科技计划项目(2006B35802004)

摘　　要：目的制备抗人肝癌免疫毫微球,观察其活性及抗癌效果。方法抗人肝癌单克隆抗体HAb18通过异型双功能交联剂SPDP与载阿霉素(ADR)人血清白蛋白毫微球[HSA(ADR)-NS]偶联,制成抗人肝癌免疫毫微球HAb18-HSA(ADR)-NS,使用凝集试验及免疫荧光检测其活性,光镜和电镜下观察其与人肝癌细胞株SMMC-7721特异性结合。MTT法检测该免疫毫微球的体外杀伤性。于人肝癌裸鼠模型上分别使用HAb18-HSA(ADM)-NS、HSA(ADM)-NS及ADM,检测3者的肿瘤抑制率。结果HAb18-HSA(ADM)-NS具有单抗活性,能与肝癌细胞特异结合;其体外杀伤SMMC-7721细胞IC50值为44.6μg/ml,与HSA(ADM)-NS(345.5μg/ml)及ADM(365.5μg/ml)相比,明显降低;体内肿瘤抑制率比HSA(ADM)-NS及ADM明显增强(P<0.001)。结论HAb18-HSA(ADM)-NS具有免疫活性,对肝癌细胞有主动靶向性,体内外均具有比HSA(ADM)-NS及ADM更强的抗癌效果。Objective To prepare nanospheres coupled with the anti-human liver cancer monoclonal antibody HAb18 and evaluate its immunoreactivity and antitumor effects. Methods The nanosphere coupled with the antibody was prepared by intermolecular cross-linking the anti-human liver cancer monoclonal antibody, HAb18, with human serum albumin nanospheres containing ADM [termed HAS（ADM）-NS] via a new hetero-bifunctional cross-linker SPDP. Condensation test and immunofluorescence assay were used to evaluate the immunoreactivity of the nanospheres, and specific binding of HAb18-HAS（ADM）-NS with liver cancer cell line SMMC-7721 was observed with optical and electron microscopes. The specific cytotoxic effects on the target cells were evaluated in vitro by MTT assay. HAb18-HAS（ADM）-NS, HAS（ADM）-NS and ADM were injected separately into nude mice bearing human liver carcinoma to evaluate the inhibitory activity of HAb18-HAS（ADM）-NS in vivo. Results The immunoreactivity of HAb18-HAS（ADM）-NS was well preserved. HAb18-HAS（ADM）-NS could bind specifically with the SMMC-7721 cells. The IC50 of HAb18-HAS（ADM）-NS against SMMC-7721 cells was 44.6 μg/ml, lower than that of HAS（ADM）-NS （345.5 μg/ml） and ADM （365.5 μg/ml）. The inhibition rate of HAb18-HAS（ADM）-NS on the growth of liver cancer xenografts was significantly higher than that of HAS（ADM）-NS and ADM （P〈0.001）. Conclusion HAb18-HAS（ADM）-NS has immunoreactivity and can actively and specifically target the liver cancer cells. The antitumor activity of HAb18-HAS（ADM）-NS is significantly higher than that of HAS（ADM）-NS and ADM.

关 键 词：免疫毫微球 人血清白蛋白毫微球 单克隆抗体 肝癌 阿霉素 

分 类 号：R735.7[医药卫生—肿瘤]