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Research Article

载于ZSM-5纳米沸石上的肿瘤抑制因子MiR-34a在肝细胞癌中的作用：体内和体外方法

卷 19, 期 5, 2019

页: [342 - 354] 页: 13

弟呕挨: 10.2174/1566523219666191108103739

价格: $65

摘要

背景：MicroRNA调节疗法已显示出治疗肝细胞癌（HCC）的巨大希望，但是有效的组织特异性和安全递送仍然是主要挑战。 目的：我们试图开发一种无机-有机混合载体，用于全身性递送抑癌药miR-34a，并研究所递送的miR-34a在体外和体内治疗肝癌的效率。 方法：在本研究中，将表达miR-34a的pEGP-miR克隆和表达载体与聚乙烯亚胺（PEI）静电结合，然后加载到ZSM-5沸石纳米颗粒（ZNP）上。通过GFP筛选和qRT-PCR分别对miR-34a构建体在HepG2细胞中的转染效率进行了定性和定量评估。通过体外和体内qRT-PCR研究miR-34a靶基因的表达。 结果：ZNP / PEI / miR-34a纳米制剂可以有效地传递到HepG2细胞中，具有较低的细胞毒性，表明生成的纳米沸石具有良好的生物相容性。此外，在HCC诱导的雄性Balb-c小鼠中，五次注射的ZNP / PEI / miR-34a纳米制剂的剂量不仅显着降低了甲胎蛋白水平和肝酶活性，而且还显着抑制了肿瘤的生长并改善了细胞结构，与阳性对照组相比。此外，注射的ZNP / PEI / miR-34a纳米制剂导致CD44和c-Myc水平显着下降。结果还显示，ZNP / PEI / miR-34a纳米制剂可在体内和体外抑制几种靶癌基因，包括AEG-1和SOX-9。 结论：我们的结果表明，miR-34a是HCC治疗的有力候选者，而AEG-1和SOX-9是miR-34a在HCC中的新靶向靶标。结果还表明，我们的纳米制剂可作为miR-34a修复用于HCC治疗以及通常用于安全基因递送的候选方法。

关键词: 肝细胞癌，抑癌药miRNA，替代疗法，纳米沸石，基因递送，靶向肿瘤。

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