Osteoporosis presents a marked global public health challenge, characterized by deficient osteogenesis and a deteriorating immune microenvironment. Conventional clinical interventions primarily target osteoclast-mediated bone damage, yet lack a comprehensive therapeutic approach that balances bone formation and resorption. Herein, we introduce a bone-targeted nanocomposite, A-Z@Pd(H), designed to address these challenges by integrating diverse functional components. The nanocomposite incorporates internal hydrogen-carrying nanozymes, which effectively scavenge multiple reactive oxygen species (ROS) and synergistically engage the autophagy–lysosome pathway to accelerate endogenous ROS degradation in macrophages. This mechanism disrupts the vicious cycle of autophagic dysfunction–ROS accumulation–macrophage inflammation. In addition, external metal–organic frameworks release zinc ions (Zn2+) in response to the acidic osteoporotic environment, thereby promoting osteogenesis. In a murine model of osteoporosis, intravenous administration of A-Z@Pd(H) leads to preferential accumulation in the femur, thereby remodeling the osteoporotic microenvironment through immune regulation, osteogenesis promotion, and osteoclast inhibition. These findings suggest that this system composed of hydrogen therapy and ion therapy may be a promising candidate for bone-targeted comprehensive therapy in osteoporosis.
Insulin resistance and pancreatic β -cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H 2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet β -cell and enhanced pancreatic β -cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.
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