Prevention of hepatic ischemia-reperfusion injury by reactive oxygen species-responsive nanozymes

Hepatic ischemia-reperfusion injury (IRI), characterized by oxidative stress and inflammation, remains a major clinical challenge in liver transplantation and resection, leading to complications such as liver failure. We develop a redox-responsive nano-drug delivery platform (PMON@Pt) by doping degradable tetrasulfide bonds into mesoporous organosilica nanoparticles (MONs), modifying their surface with a reactive oxygen species (ROS)-sensitive phenylboronic acid pinacol ester (PBAP), and incorporating platinum nanoparticles (Pt NPs) with multi-enzyme mimetic antioxidant activity. PMON@Pt enables selective Pt NP release in oxidative environments and efficiently scavenges various ROS, including superoxide radicals (O₂^•-), hydroxyl radicals (•OH), and hydrogen peroxide (H₂O₂), thereby alleviating oxidative damage, suppressing inflammation, and reducing apoptosis in vitro. In a rat hepatic IRI model, PMON@Pt demonstrates favorable passive liver targeting, specific uptake by Kupffer cells and hepatocytes, and effective suppression of inflammatory cascades, resulting in marked liver protection. Overall, PMON@Pt presents a safe, biodegradable, and ROS-responsive nanozyme delivery system with potent therapeutic potential against hepatic IRI, offering valuable insights for the rational design of inflammation-targeted nanomedicines.