Cascade nanozymes as ROS scavengers for the treatment of aseptic inflammation

Aseptic inflammatory diseases, including autoimmune disorders and chronic tissue injuries, pose significant health challenges globally, with ROS playing a key pathogenic role. While nanozymes have been explored as ROS scavengers for anti-inflammatory therapy, their clinical application is limited by suboptimal catalytic performance. Recent advances focus on cascade nanozymes, which integrate multiple enzymatic activities to mimic natural metabolic pathways. These cascade nanozymes are classified into linear, triangular, cyclic, orthogonal, and parallel configurations, each offering distinct advantages in spatial organization and sequential reaction control. Cascade nanozymes combine the stability and reusability of traditional nanozymes with enhanced catalytic efficiency, reducing diffusion barriers and improving intermediate utilization. By precisely modulating inflammatory responses, they mitigate oxidative stress and cytokine overproduction while preserving host defense mechanisms. This review highlights technological progress, applications, challenges, and future directions in cascade nanozyme development, paving the way for improved functional validation and therapeutic innovation.