Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand.
Molecules. 2020 Jun 10;25(11):2692. doi: 10.3390/molecules25112692.
RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient's therapeutic response.
RNA 干扰 (RNAi) 使用小干扰 RNA (siRNA) 在细胞中介导基因沉默，代表了癌症治疗的一种新兴策略。成功的 RNAi 介导的基因沉默需要克服多种生理障碍，以实现 siRNA 在体内有效递送至细胞，包括递送至肿瘤和/或肿瘤微环境 (TME) 中的宿主细胞。因此，已经开发了基于脂质和聚合物的纳米颗粒 siRNA 递送系统来克服这些生理障碍。在本文中，我们综述了促进 siRNA 在循环系统中存活、siRNA 从血液进入组织和 TME、靶向 siRNA 递送至肿瘤或特定细胞类型、细胞摄取以及从内涵体降解中逃逸的策略。我们还讨论了各种类型的脂质和聚合物载体在癌症治疗中的应用，包括一个关于通过 siRNA 增强的抗肿瘤纳米疫苗的部分。最后，我们综述了当前和最近使用负载 siRNA 的 NPs 进行癌症治疗的临床试验。siRNA 癌症治疗领域正在迅速发展，可以想象，精准癌症治疗可能在不久的将来受益于癌症治疗的联合使用，例如免疫检查点阻断与基因靶向 siRNA 联合使用，以增强和微调患者的治疗反应。
