Study of functional lipid nanoparticles for mRNA delivery using new ionizable tocopherol derivatives

Abstract

In this study, tocopherol-derived ionizable lipids were synthesized to create functional lipid nanoparticles for mRNA delivery. Tocopherol succinate is considered a biocompatible material because it has anti-cancer effects and degrades into vitamin E in the body. Two types of new ionizable tocopherol derivative lipids (DMT and AIT) were synthesized by introducing ionizable functional groups. The synthesized tocopherol lipids were used to make lipid nanoparticles with helper lipid, cholesterol, and PEG-DMG. The DMT LNP showed high mRNA encapsulation efficiency. Using HeLa cell lines, it was confirmed that gene transfection efficiency was increased approximately 2-fold in DMT LNP-treated cells compared to that of MC3 LNP. The two types of tocopherol derivative lipids exhibited high cell viability of over 90%, confirming very low levels of toxicity. The results of this study confirmed that lipid nanoparticles using newly developed ionizable tocopherol derivatives have potential as biocompatible and effective mRNA delivery vehicles.