碳酸酐酶Ⅸ抗体修饰去甲斑蝥素纳米胶束的肺靶向性研究  

Study on Lung targeting of carbonic antibody Ⅸ modified norcantharidin nano-micelle

作　　者：王琳[1,2] 张雅娟[1] 杨智钧[3] 陆丹玉[1] 方晨[3] 徐秋萍[4] 

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

出　　处：《中药药理与临床》2017年第1期52-56,共5页Pharmacology and Clinics of Chinese Materia Medica

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年江苏省高校"青蓝工程"优秀骨干教师培养对象资助项目

摘　　要：目的:制备碳酸酐酶Ⅸ抗体修饰的去甲斑蝥素纳米胶束(anti-CA IX NCTD nano-micelle),探讨并比较其与普通去甲斑蝥素纳米胶束(NCTD nano-micelle)的抗肿瘤作用。方法:将碳酸酐酶Ⅸ抗体孵化修饰去甲斑蝥素纳米胶束,考察其载药率、包封率、粒径等指标;通过MTT法考察去甲斑蝥素及载药胶束对A549的细胞生存率为细胞摄取实验剂量设置提供依据;取荷瘤裸鼠分别尾静脉注射去甲斑蝥素和载药胶束,并观察裸鼠的饮食,精神状态,每周用游标卡尺测量肿瘤的大小,绘制肿瘤生长曲线。结果:制备的碳酸酐酶Ⅸ抗体修饰的去甲斑蝥素纳米胶束呈圆球状,载药量为(1.26±0.03)%,包封率为(80.93±1.01)%,粒径和Zeta电位分别为146.5±48.9nm,-(14.79±0.67)mv;去甲斑蝥素及载药胶束对肿瘤细胞的抑制作用呈剂量和时间依赖性,载药胶束对肿瘤细胞的抑制作用明显优于游离药物,且anti-CA IX NCTD nano-micelle对A549的抑制率优于NCTD nano-micelle。结论:去甲斑蝥素纳米胶束经碳酸酐酶Ⅸ抗体修饰后能达到主动靶向的效果,同时能与去甲斑蝥素协同抑瘤,起到一举多得的目的。Objective： To prepare carbonic antibody Ⅸ modified norcantharidin nano-micelle（ anti-CA IX NCTD nano-micelle） and compare antiCA IX NCTD nano-micelle with NCTD nano-micelle.Methods： anti-CA IX was thiolated to incubate with NCTD nano-micelle and prepare anti-CA IX NCTD nano-micelle.The Loading Capacity（ LC）,Entrapment Efficiency（ EE） and particle distribution were investigated,respectively.The cell viability of NCTD and drug-loading nano-micelle to A549 were studied by MTT Assay in order to provide base line of uptake dosage.In vitro anti-tumor activity of NCTD and nano-micelles were evaluated in nude mice bearing A549 with inhibition rate on tumor weight.Result： The anti-CA IX NCTD nano-micelle was round and its LC,EE,size and Zeta potential were（ 1.26 ± 0.03） %,（ 80.93 ±1.01） %,146.5 ± 48.9nm and-（ 14.79 ± 0.67） mv,respectively.Cancer cell growth inhibitory effects depended on the change of drug concentrations and incubation time.Cancer cells were more sensitive to drug-loading nano-micelles than NCTD.Compared with NCTD nanomicelle,the enhanced inhibition to A549 of anti-CA IX NCTD nano-micelle was stronger.Conclusions： NCTD-loading nano-micelle modified by anti-CA IX displayed active targeting characteristics and significant antitumor effect.

关 键 词：去甲斑蝥素 碳酸酐酶Ⅸ 单克隆抗体 纳米胶束 抗肿瘤 

分 类 号：R943[医药卫生—药剂学]