索拉非尼免疫毫微球的制备及其抗肝癌效果的实验研究  

Preparation and antitumor effects of immunonanospheres containing sorafenib against human liver cancer in vitro and in vivo

作　　者：舒苗江 阚和平[1] 袁琳[1] 谭永法[1] 周杰[1] 

机构地区：[1]南方医科大学南方医院肝胆外科,510515

出　　处：《现代消化及介入诊疗》2014年第2期76-78,84,共4页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：广东省自然科学基金(S2012020010942)

摘　　要：目的制备抗人肝癌抗体与索拉非尼偶联免疫毫微球,观察其特性及抗肝癌效果。方法通过异型双功能交联剂SPDP,将抗人肝癌单克隆抗体HAb18与索拉非尼(sorafenib,SAF)人血清白蛋白毫微球[HSA(SAF)-NS]偶联,制成抗人肝癌抗体与索拉非尼偶联免疫毫微球HAb18-HSA(SAF)-NS,使用凝集试验检测其活性,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(SAF)-NS、HSA(SAF)-NS及SAF,检测三者的肿瘤抑制率。结果 HAb18-HSA(SAF)-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IC 50值为42.4μg/mL,与HSA(SAF)-NS(368.9μg/mL)及SAF(377.5μg/mL)相比,明显降低;体内肿瘤抑制率比HSA(SAF)-NS及SAF显著增强(P<0.001)。结论 HAb18-HSA(SAF)-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(SAF)-NS及SAF更强的抗癌效果。Objective To prepare immunonanospheres containing sorafenib[HAb18-HSA（SAF）-NS] a-gainst human liver cancer and evaluate its immunoreactivity and effects on cancer. Methods HAb18-HAS （SAF）-NS was prepared by intermolecular cross-linking the monoclonal antibody HAb18 with human serum albumin nanospheres containing SAF [HAS （SAF）-NS]via a new heterobifunctional cross-linker SPDP. Con-densation test and immunofluorescence assay were used to evaluate the immunoreactivity, and the specific binding of HAb18-HSA （SAF）-NS with liver cancer cell line SMMC-7721 was observed by microscope and electron-microscope. The specific cytotoxic effects on target cells were evaluated in vitro by MTT assay. HAb18-HSA（SAF）-NS, HSA（SAF）-NS and SAF were separately injected into nude mice bearing human liv-er carcinoma to observe the inhibitory activity of HAb18-HSA（SAF）-NS in vivo. Results The immunoreac-tivity of HAb18-HSA （SAF）-NS was well preserved. Under electron-microscope, HAb18-HSA （SAF）-NS could bind SMMC-7721 cells specifically. IC50 value for HAb18-HSA（SAF）-NS on SMMC-7721 cells was 42.4μg/mL, which was lower than that of HSA （SAF）-NS （368.9 μg/mL） and SAF （377.5 μg/mL）. The in-hibitory rate of HAb18-HSA （SAF）-NS on the growth of liver cancer xenografts was significantly higher than that of HSA （SAF）-NS or SAF （P〈0.001）. Conclusion HAb18-HSA （SAF）-NS has immunoreactivity and specific targeting to the liver cancer cells. The anticancer ability of HAb18-HSA （SAF）-NS is significantly higher than that of HSA（SAF）-NS and SAF.

关 键 词：免疫毫微球 索拉非尼 单克隆抗体 肝癌 

分 类 号：R392-33[医药卫生—免疫学]