载miR-15-a基因纳米复合物的制备及其抗前列腺癌作用的体外研究

发布时间：2018-02-12 23:07

本文关键词： 聚阳离子载体前列腺癌 miR--a　出处：《中国药学杂志》2017年03期 　论文类型：期刊论文

【摘要】：目的基于二硫键交联合成精氨酸-组氨酸(HRss)阳离子聚合物,构建新型纳米复合物HRss/miR-15-a,用于前列腺癌研究。方法利用~1H-NMR鉴定HRss2/miR-15-a载体的结构,通过电位粒度仪测定纳米复合物的电位和粒径,利用琼脂糖凝胶电泳考察载体对miR-15-a的包裹能力。以体外培养的前列腺癌干细胞RC-92a/h TERT为研究对象,CCK8法检测3种纳米复合物对细胞增殖的抑制作用,以p EGFP为报告基因考察基因转染效率,利用Transwell小室考察HRss/miR-15-a对细胞运动能力的影响。结果细胞毒性试验结果显示,载体材料对正常及肿瘤细胞毒性较低,可以包裹miR-15-a形成稳定的纳米复合物,HRss2/miR-15-a相较于HRss1/miR-15-a和HRss3/miR-15-a,转染效率更高,对前列腺癌干细胞的运动能力影响也更大。结论 HRss可以运载基因药物,体外评价效果最佳的HRss2,有潜力成为抗前列腺癌基因治疗中的新型载体。
[Abstract]:Objective to synthesize arginine-histidine (HRSS) cationic polymer based on disulfide bond crosslinking, and to construct a novel nanocomposite HRSS / miR-15-a for prostate cancer research. Methods the structure of HRss2/miR-15-a carrier was identified by 1H-NMR. The potential and particle size of nanocomposites were measured by potentiometric particle size analyzer. Agarose gel electrophoresis was used to investigate the encapsulation ability of the carrier to miR-15-a. The inhibitory effects of three nanocomposites on the proliferation of prostate cancer stem cells RC-92a/h TERT were detected by CCK8 method. The efficiency of gene transfection was evaluated by using p EGFP as reporter gene, and the effect of HRss/miR-15-a on cell motility was investigated by Transwell chamber. Results the cytotoxicity test showed that the carrier material was less toxic to normal and tumor cells. Compared with HRss1/miR-15-a and HRSS 3 / miR-15-a, the transfection efficiency of HRss2 / miR-15-a was higher than that of HRss1/miR-15-a and HRSS 3 / miR-15-a, and the effect on the motor ability of prostate cancer stem cells was also greater. Conclusion HRss can carry gene drugs. HRSS 2, which has the best effect in vitro, has the potential to be a novel vector in gene therapy of prostate cancer.
【作者单位】：嘉兴市妇幼保健院;嘉兴学院医学院;上海市第一人民医院;
【基金】：国家自然科学基金资助项目(81201809) 浙江省公益性技术应用研究计划资助项目(2015C37125) 浙江省自然科学基金资助项目(LQ12H30005) 嘉兴市科技计划资助项目(2012AY1075-3,2015AY23064) “十二五”浙江省高校重点学科(药理学)资助项目
【分类号】：R943;R96

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