Atomically engineered asymmetric nanozymes with enhanced photothermal-catalytic performance for periodontitis therapy and tooth whitening.

Conventional periodontitis treatments are constrained by challenges such as antibiotic resistance and inadequate tissue regeneration. Herein, we rationally engineer a robust Fe/Mn bimetallic nanozyme (Fe/Mn-Bzyme) derived from a zeolitic imidazolate framework-8 precursor, featuring atomically asymmetric Fe-Mn dual-atom active sites with the Mn1-Fe1-O1-Mn1-N3 coordination environment meticulously embedded within a nitrogen-doped carbon matrix. This tailored structure endows the nanozyme with peroxidase-like (POD) activity, which is synergistically amplified by robust near-infrared (NIR) photothermal conversion. The NIR-driven localized heating dramatically accelerates catalytic kinetics, orchestrating a tunable burst of hydroxyl radical (•OH) generation from endogenous H2O2, which confers robust antibacterial action against Porphyromonas gingivalis (99.47% ± 0.23%) and methicillin-resistant Staphylococcus aureus (99.52% ± 0.27%). Additionally, Fe/Mn-Bzyme demonstrates proactive bioactivity, promoting osteogenic differentiation of pre-osteoblasts and fostering a pro-angiogenic microenvironment. In a rat periodontitis model, a topical Fe/Mn-Bzyme ointment effectively eliminated infections, suppressed pro-inflammatory cytokine expression, mitigated systemic inflammation, and inhibited osteoclast activity, thereby creating a pro‑regenerative microenvironment conducive to subsequent periodontal tissue healing. Furthermore, its robust catalytic activity enabled superior, enamel-preserving tooth whitening compared to conventional H2O2. This work presents a versatile nanozyme platform that integrates synergistic antibacterial, anti-inflammatory, and pro-regenerative functions, offering a powerful strategy for managing complex oral diseases. STATEMENT OF SIGNIFICANCE: The significance of this work lies in the rational design of an atomically dispersed bimetallic nanozyme that harnesses synergistic photothermal-catalytic effects for integrated oral disease management. The Fe/Mn-Bzyme outperforms conventional single-function therapies, offering a powerful and translatable strategy that simultaneously addresses infection, inflammation, tissue destruction, and aesthetic concerns.