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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\u2010targeting antioxidants with excellent bioavailability and biocompatibility are yet to be developed. Herein, self\u2010assembling nanoparticles (NPs) composed of amphiphilic polymers are introduced to encapsulate organic Selenium compound L\u2010Se\u2010methylselenocysteine (SeMC) and form SeMC NPs, which protect the viabilities and functions of cultured hepatocytes in drug\u2010 or chemical\u2010induced acute hepatotoxicity models via efficient ROS removal. After further functionalization with the hepatocyte\u2010targeting ligand glycyrrhetinic acid (GA), the resultant GA\u2010SeMC NPs exhibit enhanced hepatocyte uptake and liver accumulation. In mouse models of ALI induced by acetaminophen (APAP) or carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>), treatment with GA\u2010SeMC 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\u2010targeting drug delivery strategy for the prevention and treatment of hepatic diseases.<\/jats:p>","DOI":"10.1111\/cpr.13494","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T07:41:29Z","timestamp":1683186089000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Preventing acute liver injury via hepatocyte\u2010targeting nano\u2010antioxidants"],"prefix":"10.1111","volume":"56","author":[{"given":"Xuejiao","family":"Yuan","sequence":"first","affiliation":[{"name":"College of Chemistry and Materials Science, The Education Ministry Key Lab of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis Shanghai Normal University  Shanghai 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