M2 Macrophage-Mimetic Metal-Organic Framework Nanozyme With Visible-Light-Driven Hydrogen Evolution for Uveitis Therapy

Uveitis poses a severe threat to vision and represents a critical clinical challenge. Conventional therapeutic approaches often exhibit limited efficacy in controlling disease progression and lack efficient mechanisms for managing localized oxidative stress. Given that molecular hydrogen (H 2 ) holds substantial promise for treating oxidative and inflammatory diseases via its selective antioxidant properties, we report a metal–organic framework (MOF) nanozyme-based hydrogen nanogenerator. This system integrates photocatalytic visible-light-triggered H 2 generation with multi-enzyme-like antioxidant functions for targeted uveitis management. The engineered Pt-embedded MOF nanozymes (Pt@MOF) concurrently catalyze hydrogen evolution under visible light and display superoxide dismutase- and catalase-like activities, achieving comprehensive scavenging of overproduced reactive oxygen species (ROS). Furthermore, camouflaging the nanozyme with M2 macrophage-derived cell membrane vesicles (CMVs) endows the nanoplatform with active inflammation-targeting ability, thereby enhancing the accumulation in inflamed ocular tissues. Following topical administration, this biomimetic nanomedicine successfully mitigates oxidative stress and suppresses pro-inflammatory cytokines both in vitro and in a rat model of acute uveitis. Overall, this study underscores the immense potential of integrating light-driven hydrogen therapy with nanozyme therapy, offering a highly effective strategy that could revolutionize future therapeutic interventions for inflammatory eye diseases.