Nanozymes for Liver Disease Therapy: Advances in Catalytic Activity, Targeting Strategies, and Clinical Translation.

Natural and artificial enzymes have emerged as promising candidates for biomedical applications, possessing the potential to address redox imbalances and metabolic disorders in liver diseases. However, their clinical translation remains limited by challenges in biocompatibility, targeted delivery, dose-response balance, and long-term stability. Nanozymes, novel nanomaterials with potent enzyme-like catalytic activity, exhibit promising capacities to overcome these challenges. In this review, we discuss nanozymes applied to liver diseases, including metabolic disorders, tissue repair, hepatic tumors, and viral infections. Under physiological and pathological liver conditions, diverse targeting strategies can be applied for the precise delivery of nanozymes. We demonstrate the fundamental mechanisms of nanozymes in scavenging reactive oxygen species (ROS), alleviating oxidative stress, and remodeling the immune microenvironment. The structural features, including size, morphology, composition, and surface modifications of nanozymes, critically influence catalytic performance and targeting efficiency at disease sites. These design criteria improve catalytic activity and reduce drug-induced toxicity, thereby achieving a balance between dosage and therapeutic effects. We highlight the Artificial Intelligence (AI)-driven revolution, in which machine learning contributes to predicting catalytic activity, optimizing structural design, and enabling intelligent applications of nanozymes. Finally, we outline the potential strategies and the limitations of nanozymes for clinical translation in liver disease therapy.