单抗导向阿霉素免疫毫微粒抗肝癌作用的机制  

The mechanism of anti-hepatoma effects of adriamycin-loaded immunonanoparticles led by monoclonal antibodies

作　　者：李云春[1] 蔡美英[2] 刘晓波 匡安仁[1] 梁正路[1] 

机构地区：[1]四川大学华西医院核医学科,成都610041 [2]四川大学华西医院基础医学院免疫教研室,成都610041

出　　处：《中国药理学通报》2001年第4期463-466,共4页Chinese Pharmacological Bulletin

基　　金：卫生部科研基金资助 No 98 1 2 2 5

摘　　要：目的　研究抗人肝癌单克隆抗体HAb18为导向载体的阿霉素 (ADR )人体白蛋白 (HSA)免疫毫微粒HAb18 ADR HSA NP抗肝癌作用的机制。方法　利用激光共聚焦仪和透射电镜观察HAb18 ADR HSA NP在人肝癌细胞SMMC 772 1中的内化作用 ,通过扫描电镜和透射电镜观察HAb18 ADR HSA NP对SMMC 772 1多药耐药株 (SMMC 772 1/MDR+ )的结合和内化现象 ,采用四甲基偶氮唑蓝比色法测定HAb18 ADR HSA NP对SMMC 772 1及其耐药细胞的杀伤作用。结果　HAb18 ADR HSA NP在SMMC 772 1细胞中存在内化现象 ,且该内化与温度有关 ,具抗体特异性。同时 ,HAb18 ADR HSA NP在SMMC 772 1/MDR+ 表面结合 ,并能内化 ;且其能增强SMMC 772 1/MDR+ 对ADR杀伤的敏感性。结论　HAb18 ADR HSAAIM To study the mechanism of adriamycin (ADR) loaded human serum albumin (HSA) immunonanoparticles HAb18 ADR HSA NP led by anti human hepatoma monoclonal antibodies HAb18. METHODS Internalization effects of HAb18 ADR HSA NP in human hepatoma cells SMMC 7721 were observed with laser confocal and transmission electron microscopy. The bindings and internalization of HAb18 ADR HSA NP with resistant variant of SMMC 7721 human hepatoma (SMMC 7721/MDR +) were observed with scanning electronic microscopy and transmission electron microscopy. Killing effects of HAb18 ADR HSA NP on SMMC 7721 and its resistant variant cells were determined using 5 diphenyl tetrazolium bromide colorimetric assay. RESULTS HAb18 ADR HSA NP has a internazliation in SMMC 7721 cells that relate to temperatures and has an antibody specific. Meanwhile HAb18 ADR HSA NP can bind with and internalize into SMMC 7721/MDR +, exert increased cytotoxicity to the MDR cells. CONCLUSION The mechanism of anti hepatoma effects of HAb18 ADR HSA NP is an internalization releasing drug and killing mechanism.

关 键 词：免疫毫微粒 抗肝癌作用 肝癌 单克隆抗体 阿霉素 

分 类 号：R735.7[医药卫生—肿瘤] R979.14[医药卫生—临床医学]