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

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.