mRNA vaccines represent an innovative immunization platform. However, their clinical success is critically dependent on effective delivery systems to protect the fragile mRNA and guide it into target cells. This review provides a comprehensive overview and critical comparison of prominent nanocarrier strategies, specifically regarding their application in cancer immunotherapy. Herein, four key platforms are discussed: protamine-based complexes, a foundational strategy offering intrinsic immunostimulatory properties yet limited by lower transfection efficiency. Lipid Nanoparticles (LNPs), the most clinically validated platform offering high encapsulation efficiency. Lipoplexes (LPX), a flexible alternative to LNPs featuring robust, pro-inflammatory activation favorable for personalized neo-antigen delivery. And dendritic cell (DC) vectors, an ex vivo platform offering high precision but constrained by high manufacturing costs. The present review evaluates the distinct mechanisms, advantages, and limitations of each system based on current clinical trial data in malignancies such as melanoma, prostate, and pancreatic cancer. Conclusively, the choice of delivery technology is a critical determinant that dictates the vaccine's stability, biodistribution, and the specific immune response elicited for the treatment of malignancies.
Dodopoulos et al. (2026) studied this question.
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