碳酸酐酶Ⅸ抗体在制备抗肿瘤靶向制剂中的应用  

Application of Carbonic Anhydrase Ⅸ Antibody in Preparing Anti-tumor Targeting Preparations

作　　者：王琳[1,2] 杨智钧[3] 徐秋萍[4] 

机构地区：[1]苏州卫生职业技术学院药物制剂教研室,江苏苏州215009 [2]苏州大学医学部药学院,江苏苏州215213 [3]香港浸会大学中医药学院,中国香港999077 [4]苏州市吴中区人民医院肿瘤科,江苏苏州215128

出　　处：《中国医药工业杂志》2017年第7期1035-1041,共7页Chinese Journal of Pharmaceuticals

基　　金：江苏省卫生厅资助项目<抗肿瘤药物去甲斑蝥素靶向制剂的制备研究>(JZ201402);2016年度江苏高校"青蓝工程"培养对象资助项目

摘　　要：以碳酸酐酶Ⅸ抗体(anti-CAⅨ)为靶头,采用透析法制备去甲斑蝥素纳米胶束并考察其载药率、包封率、粒径等指标及抗肿瘤靶向性。结果表明,anti-CAⅨ修饰的去甲斑蝥素纳米胶束呈圆球状,载药量、包封率、粒径和ζ电位分别为(5.26±0.03)%、(80.93±1.01)%、(146.5±48.9)nm和(-14.79±0.67)mV。去甲斑蝥素及其anti-CAⅨ修饰的胶束对A549肿瘤细胞在体外的抑制作用呈剂量和时间依赖性,载药胶束的抑制作用明显优于游离药物。荷A549肿瘤的裸鼠体内试验也表明,anti-CAⅨ修饰的去甲斑蝥素纳米胶束能显示出主动靶向效果,高剂量组(1 mg/kg)的抑瘤率达到75.65%。Carbonic anhydrase Ⅸ （CA Ⅸ） is a cell surface antigen characterized by hypoxia-induced expression in many solid tumors. This study investigated the feasibility of carbonic anhydrase Ⅸ antibody （anti-CAⅨ） modified nanomicelles for targeted delivery of norcantharidin （1） to human lung cancer cells A549 in vitro. The dialysis method was adopted to prepare anti-CA Ⅸ modified 1 nanomicelles. The results showed that the product had an encapsulation efficiency of （80.93±1.01）% and the loading capacity of （5.26±0.03）% with an average particle size of （146.5±48.9）nm and ζ potential of （-14.79±0.67）mV. In vitro antitumor activities of 1 and anti-CA Ⅸ modified 1-loaded nanomicelles were evaluated. The results showed that the inhibition effect of the anti-CA Ⅸmodified 1 nanomicelles against A549 cells was significantly higher than that of the free drug and increased in a dose- and time-dependent manner.The in vivo antitumor activity was evaluated in nude mice bearing A549 xenografts. According to the results of tumor growth inhibition, the anti-CA IX modified 1 nanomicelles demonstrated an active targeting effect. The highest tumor inhibition rate （75.65%） was founded in the high-dose （1 mg/kg） group of the modified namomicelles.

关 键 词：碳酸酐酶Ⅸ抗体 去甲斑蝥素 纳米胶束 抗肿瘤活性 

分 类 号：R944.9[医药卫生—药剂学]