Ionizable guanidine-based lipid nanoparticle for targeted mRNA delivery and cancer immunotherapy
Menée in vitro et à l'aide de modèles murins, cette étude met en évidence l'intérêt thérapeutique de nanoparticules lipidiques à base de guanidine ionisable pour le transport ciblé d'ARN messagers lors d'immunothérapies anticancéreuses
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 and antigen-specific immune responses, providing complete protection against tumor progression. In addition, intraperitoneal administration of G-LNPs enabled selective mRNA expression in the pancreas, showcasing the versatility of this delivery platform. These findings underscore the potential of guanidine-LNPs as a highly promising platform for organ-targeted mRNA delivery and cancer immunotherapy. Ionizable guanidine-based LNP achieves extrahepatic mRNA delivery and exhibits enhanced ability to activate immune cells.
Science Advances , article en libre accès, 2025