Rational design of polymer-based mRNA delivery systems for cancer treatment

Messenger RNA (mRNA)-based cancer therapeutics have shown great promise in cancer prevention and treatment, such as mRNA cancer vaccines and protein replacement therapeutics. The key to mRNA cancer therapeutics is to develop safe and effective delivery systems that can efficiently encapsulate mRNA, protect them from degradation, selectively target specific tissues, facilitate cellular uptake and endosomal escape, and ultimately release them into the cytoplasm for protein expression. Polymer-based mRNA delivery systems have received increasing attention for cancer therapy due to their virtues of customizable chemical structures, easy functionalization, and controllable stability, allowing the overcoming of tumor delivery barriers and enhancing therapeutic efficacy. This review introduces the characteristics and applications of mRNA therapeutics, the principles, and classification of polymer-based mRNA delivery systems, and summarizes several advanced mRNA delivery strategies to realize cancer-selective and intracellular delivery, organ-targeted delivery, and tissue-penetrating delivery. The review aims to provide guidance for the design of future polymer-based cancer mRNA delivery systems. This review introduces the basic design principles and recent advances in polymeric mRNA therapeutics, highlighting strategies to realize cancer-selective, organ-targeted, and tissue-penetrating mRNA delivery.