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

武鑫 蔡溱 朱全刚 王翔 王晓宇 叶丽华 刘继勇 丁雪鹰 高静 高申

中国药学杂志 ›› 2012, Vol. 47 ›› Issue (6) : 418-422.

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中国药学杂志 ›› 2012, Vol. 47 ›› Issue (6) : 418-422.
论著

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

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

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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。

Abstract

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.

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

Key words

monoclonal antibody / polyethylene glycol / dendrimer / prostatic cancer / targeting / gene vector

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武鑫 蔡溱 朱全刚 王翔 王晓宇 叶丽华 刘继勇 丁雪鹰 高静 高申 . 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[J]. 中国药学杂志, 2012, 47(6): 418-422
Targeting Gene Delivery to Prostatic Cancer with mAb-Conjugated Polyamidoamine Dendrimers[J]. Chinese Pharmaceutical Journal, 2012, 47(6): 418-422

参考文献


[1] MENDENHALL W M, HENDERSON R H, MENDENHALL N P. Definitive radiotherapy for prostate cancer [J]. Am J Clin Oncol, 2008, 31:496-503.
[2] JEMAL A, SIEGEL R, XU J, et al. Cancer statistics [J]. CA Cancer J Clin, 2010, 60(5):277-300.
[3] WU X, ZHU Q, WANG X, et al. Advances in active targeted vectors of prostate-specific membrane antigen for prostate cancer [J]. Pharm Care Res(药学服务与研究), 2011, 11(5):321-324.
[4] GONG M C, CHANG S S, SADELAIN M, et al. Prostate specific membrane antigen (PSMA)-specific monoclonal antibodies in the treatment of prostate and other cancers [J]. Cancer Metastasis Rev, 1999, 18:483-490.
[5] MOFFATT S, CRISTIANO R J. PEGylated J591 mAb loaded in PLGA-PEG-PLGA tri-block copolymer for targeted delivery: in vitro evaluation in human prostate cancer cells [J]. Int J Pharm, 2006, 317(1):10-13.
[6] WU X, DING B, GAO J, et al. Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy [J]. Int J Nanomed, 2011, 6:1747-1756.
[7] LU W, ZHANG Y, TAN Y Z, et al. Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery [J]. J Controlled Release, 2005,107(3):428-448.
[8] ELLMAN G L. Tissue sulfhydryl groups [J]. Arch Biochem Biophys, 1959, 82(1):70-77.
[9] HINSON D L, WEBBER R J. Miniaturization of the BCA protein assay [J]. Biotechniques, 1988, 6(1):14, 16, 19.
[10] DUFS C F,UCHEGBU I G, SCHCHTZLEIN A. Dendrimers in gene delivery [J]. Adv Drug Deliv Rev, 2005, 57:2177.

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)
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