Engineered metallic hybrid nanozyme for advanced inflammatory disease therapy

Inflammation poses significant therapeutic challenges due to the limitations of conventional treatments. Nanozymes, merging nanomaterial properties with enzymatic catalysis, offer promising alternatives for inflammation therapy. Among them, metallic nanozymes have attracted considerable attention due to their tunable physicochemical properties and multi-therapeutic potential. However, single-metal nanozymes suffer from insufficient catalytic efficiency, high therapeutic dosage requirements, and limited functionality, which severely hinder their clinical translation. Recent advances in metallic hybrid nanozymes, which integrate the advantages of different metallic elements, have enabled synergistic enhancement of catalytic performance and cascade effects, offering more effective solutions for inflammation treatment. In this review, we first systematically outline the fundamental principles, molecular mechanisms, and current therapeutic approaches for inflammation. Subsequently, we comprehensively discuss the definition, catalytic mechanisms, and rational design strategies of nanozymes, with a focus on the common synthesis methods, activity regulation mechanisms, computer-aided design strategies, and combination therapy approaches for metallic hybrid nanozymes. Furthermore, we provide an in-depth evaluation of the applications of metallic hybrid nanozymes in treating various inflammatory diseases. Finally, we critically analyze the key scientific challenges and future directions in the clinical translation of metallic hybrid nanozymes. This work provides a comprehensive framework for developing next-generation nanozyme therapeutics, bridging fundamental research and clinical applications in inflammation management.