(286) In vivo metabolism of cholesterol-containing nanoparticles generates immune modulatory oxysterols
Introduction: Endogenous nanometer-scale lipid particles undergo cholesterol metabolism in macrophages, generating oxidized cholesterol products (oxysterols) that are potent immune modulators associated with certain malignancies.[1] Given that the majority of clinically approved nanoparticle drugs are lipid nanoparticles (LNPs) containing cholesterol, and macrophages play a major role in LNP uptake, it is likely that LNP-associated cholesterol is metabolized by similar oxidation pathways, explaining their immune modulatory effects. Our goal is to elucidate the metabolic pathways of LNP's cholesterol.
Learning Objectives:
Determine the metabolic fate of LNP-associated cholesterol in vitro and in vivo.
Evaluate the production of oxysterols from liposomes in macrophages and different body tissues.
Understand the implication of cholesterol metabolites on immune response.