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

 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。

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

OBJECTIVE Aim to construct a novel polymer gene delivery system based on a new kind of dendrimer-polyamidoamine(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 characterize PAMAM-PEG-mAb.The cellular uptake and prostatic cancer(PCa) distribution experiments were employed to explore its biological 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 gene expression in vitro indicated that the modification of mAb could increase the gene expression efficiency and PCa targeting ability of PAMAM vectors to LNCaP(PSMA overexpressing prostate cancer cells).CONCLUSION PAMAM-PEG-mAb is a potential gene delivery vector targeting to PCa.