YPSMA-1单克隆抗体修饰的树突状高分子前列腺癌靶向基因递送载体  

Targeting Gene Delivery to Prostatic Cancer with mAb-Conjugated Polyamidoamine Dendrimers

作　　者：武鑫[1] 蔡溱[1] 朱全刚[1] 王翔[2] 王晓宇[1] 叶丽华[1] 刘继勇[1] 丁雪鹰[3] 高静[3] 高申[1] 

机构地区：[1]第二军医大学长海医院药学部,上海200433 [2]解放军第98医院药械科,浙江湖州313000 [3]第二军医大学药学院,上海200433

出　　处：《中国药学杂志》2012年第6期418-422,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30873178;30973459;81072100;81000689;81172514;81101658);上海市纳米专项(11nm0504600)

摘　　要：目的通过聚乙二醇(PEG)将YPSMA-1单克隆抗体(mAb)和聚酰胺-胺(PAMAM)连接,合成新型的前列腺癌靶向基因载体PAMAM-PEG-mAb,提高基因的转染效率和前列腺癌细胞靶向性。方法运用NMR法鉴定合成的PAMAM-PEG-mAb载体的结构,在前列腺癌细胞(PC3和LNCaP)上进行摄取实验和基因转染实验考察载体的生物学性质。结果通过结构鉴定确定PAMAM-PEG-mAb合成成功。细胞摄取实验表明,PAMAM-PEG-mAb的细胞摄取效率呈浓度依赖性。载基因后体外实验表明,PAMAM经PEG修饰后转染效率和前列腺癌靶向性无明显变化,再经mAb修饰后LNCaP细胞显著增加,而PC3细胞反而有下降。结论 PAMAM-PEG-mAb载体是一种有潜力的前列腺癌靶向基因转运载体。OBJECTIVE Aim to construct a novel polymer gene delivery system based on a new kind of dendrimer-poly- amidoamine （PAMAM）. With the modification of polyethylene glycol （PEG） and YPSMA-1 monoclonal antibody （mAb）, PAMAM- PEG-mAb was successfully synthesized as a novel gene vector targeting to the prostatic cancer. METHODS NMR was used to char- acterize PAMAM-PEG-mAb. The cellular uptake and prostatic cancer （PCa） distribution experiments were employed to explore its bio- logical characteristics and PCa cell （ PC3 and LNCaP） targeting ability. RESULTS NMR results demonstrated the successful synthesis of PAMAM-PEG-mAb. The cellular uptake of vectors was concentration-dependent. The ~ene expression in vitro indicated that themodification of mAb could increase the gene expression efficiency and PCa targeting ability of PAMAM vectors to LNCaP （ PSMA overex- pressing prostate cancer cells）. CONCLUSION PAMAM-PEG-mAb is a potential gene delivery vector targeting to PCa.

关 键 词：单克隆抗体 聚乙二醇 树突状分枝物 前列腺癌 靶向 基因载体 

分 类 号：R944[医药卫生—药剂学]