Ionizable guanidine-based lipid nanoparticle for targeted mRNA delivery and cancer immunotherapy.

ABSTRACT: The development of lipid nanoparticle (LNP) systems has largely advanced RNA therapeutics, particularly mRNA-based cancer immunotherapy. Conventional amine-LNPs, designed for hepatic RNA delivery, face challenges in targeting lymphoid organs effectively and maximize antigen presentation. In this study, we present the development of pH-responsive ionizable guanidine-LNPs (G-LNPs). Our cholesterol-free G-LNP system enables efficient delivery of mRNA to the spleen following intravenous administration. Notably, while both amine-LNPs and G-LNPs can deliver mRNA to the spleen, G-LNPs exhibit a unique ability to preferentially target antigen-presenting cells, leading to significantly enhanced antigen presentation and robust T cell activation. mRNA vaccines formulated with G-LNPs elicited strong a

SUBMITTER: Zhang H 

PROVIDER: S-EPMC12551712 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature