Killing two birds with one stone: How Au@Pt nanozyme combats liver injury through attenuating oxidative stress and countering inflammation

Acetaminophen (APAP) overdose remains a leading cause of drug-induced acute liver failure, with existing therapeutic options proving insufficient. Given the central role of oxidative stress and inflammatory cascades in APAP-induced hepatotoxicity, we developed an Au@Pt nanozyme that mimics multi-enzymatic activities—superoxide dismutase (SOD) and catalase (CAT)—to counteract oxidative damage and inflammation. This nanozyme effectively scavenges reactive oxygen species (ROS) and exhibits antiapoptotic properties, offering a promising strategy for mitigating APAP-induced liver injury. Mechanistically, Au@Pt nanozyme not only attenuates hepatic oxidative stress by suppressing ROS accumulation but also reduces the secretion of pro-inflammatory cytokines (IL-1β, IL-6) while enhancing anti-inflammatory signals (IL-10). Further investigations reveal that Au@Pt exerts its protective effects by inhibiting the chemokine and MAPK signaling pathways, thereby shielding compromised hepatocytes from secondary damage and reducing apoptosis. Importantly, in vivo assessments confirm the excellent biosafety profile of Au@Pt, with no detectable toxicity. Collectively, our findings highlight the therapeutic potential of this nanozyme for both prevention and treatment of ALI.