Metabolic–reprogrammed MnO₂–Mg/Pt@BBF nanozyme disrupts biofilm cohesion for enhanced chemodynamic therapy of periodontitis

A metabolically reprogrammed MnO₂-Mg/Pt@BBF nanozyme is developed for periodontitis treatment. • Mg²⁺ amplifies endogenous H₂O₂ production via SpxB in Streptococcus gordonii. • Pt decoration enriches catalytically active Mn²⁺ to enhance chemodynamic therapy. • Covalently immobilized BBF inhibits LuxS/AI-2 quorum sensing and disrupts biofilm cohesion. • The nanozyme reduces bacterial burden, alveolar bone loss, and inflammation in vivo . Objectives To overcome the intrinsic incompatibility between dense periodontal biofilms and chemodynamic therapy (CDT), we developed a vacancy–engineered MnO₂ nanozyme that integrates redox–state programming, Mg²⁺–enabled endogenous H₂O₂ amplification, and covalently immobilized quorum–sensing inhibition for the local treatment of periodontitis. Methods Mg²⁺–coordinated MnO₂ nanoflowers were decorated with Pt nanoparticles and covalently functionalized with BBF. Physicochemical properties, Mn valence states, H₂O₂ and ·OH generation, LuxS/AI–2 signaling, Porphyromonas gingivalis metabolomic changes, antibiofilm activity, and therapeutic efficacy in rat periodontitis were evaluated. Results Pt decoration increased the Mn²⁺ fraction from 33% to 51%, while Mg²⁺ enhanced SpxB–mediated H₂O₂ production by Streptococcus gordonii . Immobilized BBF reduced AI–2 activity from 67.8% to 22.8% and downregulated luxS, fimA, mfa1, kgp, and rgpA . In dual–species biofilms, MnO₂–Mg/Pt@BBF yielded 68.7% dead cells, an approximately 4–log₁₀ reduction in viable bacteria, and the lowest residual thickness. Metabolomics revealed depletion of G6P, R5P, NADPH, ATP, and α–ketoglutarate in P. gingivalis. In vivo , treatment reduced periodontal bacterial burden by approximately 3 orders of magnitude and decreased the CEJ–ABC distance from 1.44 ± 0.28 mm to 0.56 ± 0.15 mm, accompanied by reduced inflammation and IL-6 expression, improved collagen organization, and elevated Arg-1 levels. Significance This locally deliverable platform couples vacancy/valence–tuned catalysis, Mg²⁺–primed endogenous oxidant supply, and surface–immobilized quorum–sensing blockade, offering a composition–guided strategy for controlling polymicrobial periodontal biofilms and limiting infection–associated tissue destruction.