Multi-Enzyme Mimetic Molybdenum Nitride Nanozymes Reshape Subgingival Microenvironment for Synergistic Periodontitis Therapy via ROS Regulation and Microbiome Remodeling.

Periodontitis, a chronic inflammatory disease initiated and sustained by plaque microorganisms and host immune response, remains an intractable oral disease and a leading cause of tooth loss worldwide. Traditional mechanical debridement and adjunctive antibiotic or antiseptic therapy often shows limited efficacy due to the complex anatomical structure, concerns regarding antimicrobial resistance, and poor penetration and retention within the subgingival infection niche. To overcome this limitation, we designed a Mo-N coordinated nanozyme exhibiting synergistic mimetic activities of multiple enzymes, including peroxidase (POD)-like, oxidase (OXD)-like, and catalase (CAT)-like activity. Benefiting from Mo-N coordination and multi-enzyme mimetic behavior, Mo5N6 nanozymes dynamically modulate local oxidative reactions within the gingival sulcus, thereby effectively damaging pathogenic bacteria while avoiding excessive oxidative stress. The nanozymes efficiently suppress anaerobic Gram-negative periodontal pathogens sensitive to elevated reactive oxygen species (ROS), facilitating efficient attenuation of pathogenic stimuli. This strategy not only enhances the periodontal microenvironment but also facilitates the restoration of commensal microbiota and regeneration of periodontal tissues, highlighting the therapeutic potential of Mo5N6 nanozymes in periodontitis treatment.