세미나

Lipid nanoparticles (LNPs) are the most clinically advanced platform for nucleic acid delivery, yet their biodistribution is dominated by the liver and their design remains largely empirical. Our laboratory treats the LNP as a modular assembly in which each lipid carries a defined structural or biological function, so that changing a single component redirects the particle toward a chosen immune cell. Tricaprin and phosphatidylserine doubled uptake in macrophages while lowering it threefold in HEK293 and fivefold in 4T1 cells, and co-delivery of CpG with STAT3 siRNA transfected over 10 percent of tumor macrophages and shifted the tumor toward an M1 phenotype with more dendritic cells and CD4 and CD8 T cells. Substituting 30 percent DOTAP raised mRNA expression in NK cells from 5.9 to 62.7 percent, elongated their mitochondria, and produced anti-GPC3 CAR-NK cells with no viral vector; paired with irreversible electroporation, these cells left 3 of 5 xenograft-bearing mice tumor free and generated antigen-specific T cell memory. In a third design the lipid is the drug: a cholesterol-PEG-pheophorbide a lipid carrying GPX4 siRNA killed tumor cells by ferroptosis at a reduced light dose, and a 7-dehydrocholesterol counterpart amplified a single 6 Gy fraction with body weight unchanged. One rule connects all three. Give the lipid a second job.