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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 HSA NP抗肝癌作用的机制是其内化释药杀伤机制
Objective To study the mechanism of anti-hepatocarcinoma effect of anti-human hepatocarcinoma monoclonal antibody HAb18 as the directing carrier of adriamycin (ADR) human albumin (HSA) immune nanoparticulate HAb18 ADR HSA NP. Methods The internalization of HAb18 ADR HSA NP in SMMC 772 1 human hepatoma cells was observed by laser confocal microscope and transmission electron microscope. HAb18 ADR HSA NP was detected by scanning electron microscope and transmission electron microscopy on SMMC 772 1 multidrug resistant strain (SMMC 772). 1/MDR+ ) binding and internalization phenomenon, the killing effect of HAb18 ADR HSA NP on SMMC 772 1 and its resistant cells was determined by tetramethylazol blue colorimetry. Results HAb18 ADR HSA NPs were internalized in SMMC 772 1 cells, and the internalization was temperature-dependent and antibody-specific. At the same time, the HAb18 ADR HSA NP binds to SMMC 772 1/MDR+ surface and can be internalized; and it enhances the sensitivity of SMMC 772 1/MDR+ to ADR killing. Conclusion The mechanism of HAb18 ADR HSA NP against hepatocellular carcinoma is its mechanism of internalized drug release.