Advances in nano-delivery systems for overcoming the challenges of applying siRNA drugs in tumor therapy

Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs (siRNAs), an important class of nucleic acid drugs, can silence the mRNAs of tumor-associated genes with high specificity through RNA interference (RNAi), inhibiting tumor-related signaling pathways or protein expression and thereby exerting anti-tumor effects. However, anti-tumor siRNA drugs are currently in the clinical research stage, and none of these drugs have been approved for marketing, mainly because of the challenges in terms of safety, efficacy and targeted delivery. Nano-delivery systems can enhance siRNA stability and improve siRNA pharmacokinetics and biodistribution, while increasing their uptake by target cells to achieve precise delivery and controlled release, thereby serving as a promising solution to overcome the challenges of siRNA drug application. This review summarizes the existing research on the nano-delivery systems currently available to help siRNAs achieve organ-targeted delivery and enhance the anti-tumor efficacy of siRNAs, discussing the characteristics of siRNA action and the unique advantages of different types of nano-delivery systems. The aim was to provide novel ideas for the design and optimization of siRNA-based drug delivery and the development of novel anti-tumor formulations to promote the clinical translation and application of siRNA drugs.