Dual-Functional Microreactor Enabling Hydrogen Therapy and Mild Photothermal Therapy for Osteoarthritis Treatment.

Osteoarthritis (OA) is a prevalent degenerative joint disorder. Current therapeutic approaches have yielded suboptimal clinical outcomes, primarily due to their inability to effectively eliminate reactive oxygen species (ROS), which are the key drivers of inflammatory pathology. Molecular hydrogen (H2) has emerged as a promising therapeutic agent owing to its selective scavenging of cytotoxic ROS, thereby exerting potent anti-inflammatory effects. In this study, we propose a spatiotemporally controlled, light-activated strategy for on-demand hydrogen generation to treat OA. To realize this, we engineered a biocompatible microreactor, C3N4/Au@liposome (C3N4/Au@lip), in which a C3N4/Au photocatalyst is encapsulated within liposomal vesicles. This design enhances physiological compatibility. Under illumination, the Schottky heterojunction formed between C3N4 and gold nanoparticles (Au NPs) significantly enhanced the separation and migration efficiency of photogenerated charge carriers, thereby boosting photocatalytic hydrogen (H2) evolution. The H2 produced in situ functioned as a selective scavenger of cytotoxic ROS, leading to downregulation of pro-inflammatory cytokines (IL-6 and IL-1β). Concurrently, Au NPs leveraged localized surface plasmon resonance (LSPR) under light irradiation to induce mild photothermal therapy (MPT), which facilitated H2 diffusion into the joint lesions. Collectively, this dual-functional (Hydrogen therapy and LSPR-mediated MPT) strategy demonstrates a nanomaterial-enabled therapeutic platform with strong translational potential for inflammatory diseases.