适配体C2min介导的可靶向两种前列腺癌基因递送系统
投稿时间:2019-06-14  修订日期:2019-07-26  点此下载全文
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作者单位E-mail
张晶 内蒙古医科大学附属医院药剂部 124576779@qq.com 
顾永卫 上海维洱实验室  
武鑫 上海维洱实验室  
基金项目:国家自然基金(81072100),上海市青年科技启明星计划资助(18QB1400400)
中文摘要:目的 通过合成可靶向两种前列腺癌的基因载体PAMAM-PEG-C2min,以提高基因的转染效率和肿瘤靶向性。方法 将双功能聚乙二醇的一端与聚酰胺-胺(PAMAM)相连,另一端与适配体(C2min)连接,并利用1HNMR技术对合成的PAMAM-PEG-C2min基因载体进行结构鉴定。通过两种前列腺癌PC3和LNCaP细胞的体外摄取和基因转染实验,考察纳米复合物的生物学特性。并利用动物活体成像技术考察合成的纳米复合物的体内分布特征。结果 核磁共振结果表明,本研究成功合成了PAMAM-PEG-C2min。PC3和LNCaP 细胞对PAMAM-PEG-C2min的摄取结果体现出浓度依赖性。且与不经C2min修饰的PAMA-PEGM相比,PAMAM-PEG-C2min递药系统的基因转染效率和肿瘤细胞靶向性明显提高。体内靶向性结果表明,PAMAM-PEG-C2min可实现同时靶向2种前列腺癌组织的作用。结论 本研究合成的PAMAM-PEG-C2min递送载体具有良好的肿瘤靶向性,为前列腺癌的综合治疗和靶向治疗提供了新的技术平台。
中文关键词:适配体  靶向  激素依赖型前列腺癌  激素非依赖型前列腺癌  基因
 
The research of the C2min aptamer-modified gene delivery system for targeting ADPC/AIPC prostate cancer
Abstract:Objective The aptamer (C2min) and polyamide-amine (PAMAM) were ligated by polyethylene glycol (PEG) to synthesize a novel prostate cancer targeting gene vector PAMAM-PEG-C2min to improve gene transfection efficiency and target to prostate cancer. Methods The structure of the synthesized PAMAM-PEG-C2min was identified by NMR. The biological characteristics of the nanoparticles were examined by the uptake experiments and gene transfection experiments with the prostate cancer cells (PC3 and LNCaP). Besides, the in vivo targeting was investigated using in vivo image system. In addition, in vivo targeting results indicated that PAMAM-PEG-C2min can achieve the simultaneous targeting of two prostate cancer tissues. Results The PAMAM-PEG-C2min synthesis was confirmed by NMR. Cell uptake experiments showed that the cell uptake efficiency of PAMAM-PEG-C2min was concentration dependent. In vitro experiments showed that the PC3 and LNCaP cells transfection efficiency and targeting of PAMAM-PEG modified with C2min was significantly improved compared with the PAMAM modified with PEG. Conclusion PAMAM-PEG-C2min is a potential drug targeted delivery vehicle, providing a new technology platform for different stages and targeting treating prostate cancer.
keywords:adapter  targeting drug delivery  androgen-dependent prostate cancer  androgen-independent prostate cancer  gene
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