The Polymer Society of Korea

이현진 (충남대학교)

최준식 (충남대학교)

In this study, novel ionizable tocopherol-derived lipids were developed for lipid nanoparticle (LNP)-mediated mRNA delivery. α-Tocopherol succinate was used as a biocompatible hydrophobic scaffold, and two ionizable lipids, DMT and AIT, were synthesized by introducing different head groups. LNPs were formulated with ionizable lipid, DSPC, cholesterol, and DMG-PEG2000 at a molar ratio of 50:10:38.5:1.5. In HeLa cells, DMT LNPs achieved approximately two-fold higher luciferase expression compared to MC3-based LNPs, demonstrating enhanced mRNA delivery efficiency. In contrast, AIT LNPs showed lower encapsulation and transfection efficiency, indicating the importance of lipid structure. All LNP formulations maintained cell viability above 90%, confirming low cytotoxicity. These results suggest that DMT-based tocopherol LNPs are promising and biocompatible carriers for efficient mRNA delivery.