Lipid-based ionic liquids enable efficient messenger RNA intracellular delivery

Abstract In this study, we report novel lipid-based ionic liquids (LBILs) that enable the complexation with messenger RNA. Lipid-based ionic liquids were synthesized by combining cationic phospholipids with different alkyl chain lengths (dimyristoyl, dipalmitoyl, and distearyl) and anionic linoleate. The resulting lipid-based ionic liquid–messenger RNA complexes exhibited distinct physicochemical properties, such as particle size and zeta potential, depending on the phospholipid structure. Transfection studies in HeLa cells further revealed that the lipid-based ionic liquid prepared from the dimyristoyl-containing phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine achieved the highest gene expression efficiency. These results demonstrate that lipid-based ionic liquids represent a promising molecular platform for effective intracellular messenger RNA delivery.