Cell membrane-coated mRNA nanoparticles for enhanced delivery to dendritic cells and immunotherapy

Cationic polymers such as polyethylenimine have been considered promising carriers for mRNA vaccines. However, their application is hindered by their inherent toxicity and a lack of targeted delivery capability. These issues need to be addressed to develop effective cancer vaccines. In this study, we investigated whether dendritic cell membrane-coated polyethylenimine/mRNA nanoparticles (DPN) could effectively deliver mRNA to dendritic cells and induce immune responses. For comparison, we employed red blood cell membrane-coated polyethylenimine/mRNA (RPN) and plain polyethylenimine/mRNA polyplex (PN). The dendritic cell membrane coating altered the zeta potential values and surface protein patterns of PN. DPN demonstrated significantly higher uptake in dendritic cells compared to PN and RPN, and it also showed greater mRNA expression within these cells. DPN, carrying mRNA encoding luciferase, enhanced green fluorescent protein, or ovalbumin (OVA), exhibited higher protein expression in dendritic cells than the other groups. Additionally, DPN exhibited favorable mRNA escape from lysosomes post-internalization into dendritic cells. In mice, subcutaneous administration of DPN containing ovalbumin mRNA (DPN