Preventing acute liver injury via hepatocyte‐targeting nano‐antioxidants

Acute liver injury (ALI) is a severe liver disease that is characterized by sudden and massive hepatocyte necrosis and deterioration of liver functions. Oxidative stress is increasingly recognized as a key factor in the induction and progression of ALI. Scavenging excessive reactive oxygen species (ROS) with antioxidants has become a promising therapeutic option, but intrinsically hepatocyte‐targeting antioxidants with excellent bioavailability and biocompatibility are yet to be developed. Herein, self‐assembling nanoparticles (NPs) composed of amphiphilic polymers are introduced to encapsulate organic Selenium compound L‐Se‐methylselenocysteine (SeMC) and form SeMC NPs, which protect the viabilities and functions of cultured hepatocytes in drug‐ or chemical‐induced acute hepatotoxicity models via efficient ROS removal. After further functionalization with the hepatocyte‐targeting ligand glycyrrhetinic acid (GA), the resultant GA‐SeMC NPs exhibit enhanced hepatocyte uptake and liver accumulation. In mouse models of ALI induced by acetaminophen (APAP) or carbon tetrachloride (CCl(4)), treatment with GA‐SeMC NPs significantly decrease the levels of hepatic lipid peroxidation, tissue vacuolization and serum liver transaminases, while prominently increase that of endogenous antioxidant enzymes. Our study therefore presents a liver‐targeting drug delivery strategy for the prevention and treatment of hepatic diseases.