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在癌症治疗中实现有效的基因沉默的双重向丹德里默介导的siRNA传递系统
Yiwen Dong1, Tianzhu Yu2, Ling Ding2
1State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, Center of Advanced Pharmaceutics and Biomaterials , China Pharmaceutical University , 24 Tong Jia Xiang , 210009 Nanjing , People's Republic of China.
Journal of the American Chemical Society
|October 23, 2018
概括
这项研究引入了一种用于向小干扰RNA (siRNA) 传递给癌细胞的新型两性 dendrimer. 该系统表现出增强的基因沉默和强大的抗癌活性,没有观察到毒性,为基于RNAi的癌症治疗提供了有希望的非病毒载体.
科学领域:
- 生物技术
- 纳米技术
- 分子生物学
背景情况:
- 小干扰RNA (siRNA) 具有治疗潜力,但需要安全有效的输送系统.
- 针对性治疗对于最大限度地提高治疗效果和最大限度地降低siRNA疗法的毒性至关重要.
- 由于其多价值和自我组装特性,两性树突为siRNA传递提供了一个有前途的平台.
研究的目的:
- 开发和评估一种基于双胞胎树枝体的系统,用于向siRNA传递给癌细胞.
- 通过整合蛋白和神经平素-1受体定位瘤的双重向的有效性.
- 研究该系统保护siRNA的能力,促进内体逃生,并增强基因沉默.
主要方法:
- 用于构建siRNA/dendrimer复合物的弹道方法.
- 将双重向与RGDK弹头结合在一起,用于特定的癌细胞相互作用.
- 纳米颗粒的静电涂层以确保稳定性,siRNA保护和准部分的可访问性.
- 在体外和体内对基因沉默,抗癌活性和毒性的评估.
主要成果:
- 形成小,稳定的纳米颗粒,保护siRNA免受降解.
- 与非向系统相比,证明了增强的siRNA传递,基因沉默和抗癌活性.
- 没有观察到急性毒性或诱导炎症,这表明安全性很好.
结论:
- 在癌症治疗中开发的双胞胎 dendrimer 系统是有效的非病毒载体.
- 这种基于纳米技术的方法显示了基于RNAi的针对癌症的个性化药物的潜力.
- 这种自组装的树状分子平台提供了广泛的生物医学应用可能性.
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