Hepatocyte-targeted hyaluronic acid-polyethyleneimine conjugates for acute liver injury therapy by ROS elimination and inflammation modulation

•HA-PEI actively targets the liver through the CD44 receptor to reduce the off-target effects of PEI (highest effect at 1000 K).•This study provided a therapeutic agent for late-stage liver injury induced by acetaminophen that outperforms the FDA-approved drug N-acetylcysteine.•HA-PEI could increase oxygen content, eliminate ROS, and maintain mitochondrial membrane potential to protect hepatocytes that are under oxidative stress and inhibit the secretion of inflammatory factors to block the migration of immune cells to the liver, safeguarding hepatocytes from secondary damage.