Spontaneous hydrogen-releasing nanoenzyme alleviates osteoarthritis via oxidative stress reduction and mitochondrial dysfunction reversal

作者：Qi Wang, Minyi Zhang, Weihao Jiang, Dejian Li, Beijie Qi, Shi Shi, Shuo Shi, Shuo Shi, Shuo Shi, Chengqing Yi · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03716-0 · 被引用次数：13 · 研究领域：Hydrogen's biological and therapeutic effects、Biochemical effects in animals、Hydrogen Storage and Materials

Osteoarthritis (OA), a chronic and degenerative joint disease, has become increasingly prevalent due to the aging population, posing a significant societal burden. However, despite progress, effective therapeutic options for osteoarthritis remain limited. In OA, chronic inflammation mediates a hypoxic microenvironment, leading to increased cellular energy demands. Over time, this causes mitochondrial dysfunction, favoring the accumulation of ROS, thereby perpetuating inflammation. Furthermore, reduced autophagy in aging chondrocytes hinder the clearance of damaged mitochondria, exacerbating oxidative stress. Herein, we have developed a simple and environmentally friendly strategy to fabricate hydrogen-releasing nanozymes (Se-HMPB@AB@COS) that spontaneously release hydrogen gas, effectively treating osteoarthritis through antioxidant, anti-inflammatory, and mitochondrial dysfunction reversal mechanisms. During the process of hydrogen therapy, small hydrogen molecules can readily penetrate mitochondria, specifically reducing the levels of •OH thereby protecting mitochondrial function. Our research further unveils that hydrogen therapy can effectively enhance mitophagy and delay chondrocyte senescence. In vivo, Se-HMPB@AB@COS encapsulated with chondroitin sulfate significantly promotes the synthesis of collagen II, inhibits the degradation of extracellular matrix, and reduces inflammatory factors. Overall, this study innovatively synthesized a hydrogen-releasing nanozyme, demons...