Engineered lipid nanoparticles with synergistic dendritic cell targeting and enhanced endosomal escape for boosted mRNA cancer vaccines.

ABSTRACT: Lipid nanoparticles (LNPs) have emerged as a pivotal carriers for enhancing mRNA therapeutics, particularly in antitumor therapy. However, achieving robust antigen expression remains a major challenge due to limitations in precise targeted delivery and inefficient endosomal escape. In this study, we constructed an ambidextrous LNP to achieve robust tumor-specific antigen expression through targeted cell delivery and enhanced endosomal escape of mRNA-LNPs. To improve endosomal escape, we synthesized a novel pH-responsive PEGylated lipid designed to synergistically enhance membrane fusion effect with ionizable lipids, thereby optimizing the translation of the desired antigen. This is accomplished by promoting the early endosomal escape and endosomal recycling transport. For precise delivery

SUBMITTER: Wang S 

PROVIDER: S-EPMC12308020 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature