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 (H2) 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 H2 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.