Nanoparticle-based delivery systems have contributed to the recent clinical success of RNA therapeutics, including siRNA and mRNA. RNA delivery using polymers has several distinct properties, such as enabling RNA delivery into extra-hepatic organs, modulation of immune responses to RNA, and regulation of intracellular RNA release. However, delivery systems should overcome safety and stability issues to achieve widespread therapeutic applications. Safety concerns include direct damage to cellular components, innate and adaptive immune responses, complement activation, and interaction with surrounding molecules and cells in the blood circulation. The stability of the delivery systems should balance extracellular RNA protection and controlled intracellular RNA release, which requires optimization for each RNA species. Further, polymer designs for improving safety and stability often conflict with each other. This review covers advances in polymer-based approaches to address these issues over several years, focusing on biological understanding and design concepts for delivery systems rather than material chemistry.

基于纳米颗粒的递送系统为 RNA 疗法（包括 siRNA 和 mRNA）最近的临床成功做出了贡献。使用聚合物的 RNA 递送具有多种独特的特性，例如能够将 RNA 递送到肝外器官、调节对 RNA 的免疫反应以及调节细胞内 RNA 释放。然而，递送系统应克服安全性和稳定性问题以实现广泛的治疗应用。安全问题包括对细胞成分、先天性和适应性免疫反应的直接损害，补体激活，以及与血液循环中周围分子和细胞的相互作用。递送系统的稳定性应平衡细胞外 RNA 保护和受控细胞内 RNA 释放，这需要针对每种 RNA 进行优化。此外，用于提高安全性和稳定性的聚合物设计常常相互冲突。本综述涵盖了多年来解决这些问题的基于聚合物的方法的进展，重点关注递送系统的生物学理解和设计概念，而不是材料化学。