Current Advances in Antioxidant Nanozymes for Liver Diseases.

The liver with unique physiological functions is susceptible to oxidative stress (OS) damage from reactive oxygen species (ROS) accumulation, further triggering various liver diseases. Compared with conventional pharmacological and surgical therapies, natural antioxidant enzymes represent promise for liver disease therapy due to high ROS scavenging and low immunogenicity. However, their clinical translation is limited by instability and complex preparation. Antioxidant nanozymes not only mimic natural enzymes, but possess advantages including simple structure, low cost and high stability. They have emerged as ideal therapeutic options for liver diseases by mitigating OS, modulating inflammation, and remodeling the pathological microenvironment. This review innovatively elucidates hepatic OS pathogenesis from a synergistic perspective, integrating indirect (inflammatory pathways) and direct (organelle stress, oxidase activation) ROS generation routes, thereby filling gaps in existing literature. Subsequently, we systematically summarize advances in five representative classes of nanomaterials: metal-, selenium-, carbon-, organic- and metal-organic frameworks (MOF)-based, and emphasize catalytic mechanisms and activity regulation strategies to guide the design of effective, low-toxicity antioxidant nanozymes. Furthermore, this review highlights recent progress of antioxidant nanozymes in typical liver diseases, including drug-induced liver injury, hepatic ischemia-reperfusion injury, liver fibrosis, and acute liver failure, alongside clinical translation bottlenecks. Finally, current challenges and future perspectives for antioxidant nanozymes are outlined.