Coarse-Grained Molecular Dynamics Simulations of Lipid Nanodroplets and Endosomal Membranes: Focusing on the Fusion Mechanisms.

ABSTRACT: Lipid nanoparticles (LNPs) have received significant attention as effective RNA carriers in RNA-based therapeutics and vaccines. Particularly, ionizable lipids (ILs) of LNPs play a crucial role in endosomal escape and lipid-mediated RNA delivery owing to their pH-dependent molecular characteristics. Therefore, it is essential to enhance the endosomal escape efficiency of ILs, which is primary bottleneck in the successful cytoplasmic delivery of RNA. However, the molecular-level understanding of the roles and dynamics of ILs during the endosomal escape stage remains unclear. To elucidate this, we utilized coarse-grained (CG) molecular dynamics (MD) simulations. In this simulation, we designed lipid nanodroplets (LNDs) containing D-Lin-MC3-DMA (MC3) and ALC-0315, which have proven effective

SUBMITTER: Go YJ 

PROVIDER: S-EPMC12732718 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature