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

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.