A Pt-Co paired-site nanozyme with a triple-synergistic action enhances periodontitis therapy

Nanozymes have emerged as promising therapeutic agents, but clinical translation remains hindered by limited catalytic efficiency, structural disorder, and single-function activity. An atomic-level ordered platinum-cobalt (Pt-Co) nanozyme was designed to overcome these limitations, achieving enhanced catalytic performance and multifunctional bioactivity. The highly uniform L1₀-type Pt-Co structure, featuring strong electronic coupling and lattice strain effects between Pt and Co, synergistically lowers reaction energy barriers, thereby significantly enhancing superoxide dismutase (SOD)- and catalase (CAT)-like activities for rapid scavenging of reactive oxygen species (ROS), as evidenced by 82% SOD-like inhibition (vs. 46% for Pt-C catalysts) and a doubled H₂O₂ decomposition rate. In vitro and in vivo studies demonstrated that the nanozyme attenuated ROS-induced inflammation by shifting macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 (ROS-positive macrophages decreased from 98.1% to 29.5%), reducing inflammatory cytokine production and activating nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor kappa-B (NF-κB) signaling. Moreover, Co endowed the nanozyme with osteogenic capabilities by upregulating osteogenic gene expression, including a twofold increase in Runx2, substantially promoting bone regeneration in a mouse model of periodontitis. The dual-metal nanozyme thus serves as a versatile therapeutic platform, simultaneously addressing ROS accumulation, inflammation, and bone resorption, and offers a promising advance in the treatment of periodontitis and other oxidative stress-related diseases.