Department of Biomedical Engineering Indian Institute of Technology Hyderabad, Kandi 502284, India.
Mol Pharm. 2022 Dec 5;19(12):4506-4526. doi: 10.1021/acs.molpharmaceut.2c00811. Epub 2022 Nov 21.
RNA interference (RNAi) has increased the possibility of restoring RNA drug targets for cancer treatment. Small interfering RNA (siRNA) is a promising therapeutic RNAi tool that targets the defective gene by inhibiting its mRNA expression and stopping its translation. However, siRNAs have flaws like poor intracellular trafficking, RNase degradation, rapid kidney filtration, off-targeting, and toxicity, which limit their therapeutic efficiency. Nanocarriers (NCs) have been designed to overcome such flaws and increase antitumor activity. Combining siRNA and anticancer drugs can give synergistic effects in cancer cells, making them a significant gene-modification tool in cancer therapy. Our discussion of NCs-mediated siRNA delivery in this review includes their mechanism, limitations, and advantages in comparison with naked siRNA delivery. We will also discuss organic NCs (polymers and lipids) and inorganic NCs (quantum dots, carbon nanotubes, and gold) that have been reported for extensive delivery of therapeutic siRNA to tumor sites. Finally, we will conclude by discussing the studies based on organic and inorganic NCs-mediated siRNA drug delivery systems conducted in the years 2020 and 2021.
RNA 干扰 (RNAi) 增加了恢复癌症治疗中 RNA 药物靶点的可能性。小干扰 RNA (siRNA) 是一种很有前途的治疗性 RNAi 工具,通过抑制其 mRNA 表达并阻止其翻译来靶向缺陷基因。然而,siRNA 存在一些缺陷,如细胞内运输不良、RNase 降解、快速肾脏过滤、脱靶和毒性,这些缺陷限制了其治疗效率。纳米载体 (NC) 的设计旨在克服这些缺陷并提高抗肿瘤活性。siRNA 和抗癌药物的联合使用可以在癌细胞中产生协同作用,使它们成为癌症治疗中重要的基因修饰工具。我们在这篇综述中讨论了 NC 介导的 siRNA 递送来包括它们的机制、局限性和与裸 siRNA 递送相比的优势。我们还将讨论已报道的用于将治疗性 siRNA 广泛递送到肿瘤部位的有机 NCs(聚合物和脂质)和无机 NCs(量子点、碳纳米管和金)。最后,我们将讨论基于有机和无机 NCs 介导的 siRNA 药物递送系统的研究,这些研究是在 2020 年和 2021 年进行的。