Lipid nanoparticles and compositions thereof are disclosed herein. An exemplary nanoparticle composition includes an ionizable lipid, a phospholipid, a PEG-lipid, and a cholesterol modified with a hydroxyl group near the D-sterol ring. The disclosed nanoparticle compositions can target liver Kupffer cells and endothelial cells more preferentially than hepatocytes which should be beneficial in treating liver diseases in which dysfunctional Kupffer cells and endothelial cells are involved in disease pathogenesis.
