Nanoparticles Targeting Hepatic Stellate Cells for the Treatment of Liver Fibrosis

Liver fibrosis is a scarring process that can progress to cirrhosis, the primary cause for hepatocellular carcinoma.Although various anti-fibrotic agents have been explored for liver fibrosis treatment, their clinical applications have been limited due to insufficient delivery of the agents to target cells and toxicity.Hepatic stellate cells (HSC) play key roles in the development of liver fibrosis because they produce extracellular matrix proteins, such as collagens, when activated upon liver injury.Therefore, surface engineering of organic nanoparticles (such as liposomes, polymeric, and lipid nanoparticles) with ligands specific to the overexpressed receptors secreted by activated HSC during hepatic fibrogenesis has been exploited in the last decade to develop effective approaches to reverse liver fibrosis.Passive targeting has also been explored as a potential strategy to deliver anti-fibrotic agents to activated HSC through systemic administration of non-ligand nanoparticles, including both organic (polymeric and lipid) and inorganic (mesoporous silica, cerium oxide and silver) nanoparticles.This review focuses on the most recent literatures concerning different types of nanoparticles for liver fibrosis treatment via HSC-targeting delivery of various anti-fibrotic agents by the two strategies aforementioned, with special emphasis on their therapeutic mechanisms and biological efficacies at both cellular and the whole body levels.