Apical periodontal endodontitis (AP) is an inflammatory disease caused by persistent root canal biofilms. Its treatment remains challenging because traditional root canal therapy sometimes fails to achieve effective disinfection and tissue regeneration. In this study, a multifunctional bimetallic ion-modified metal-organic framework (MOF) nanozyme composite material, MOF-FeAg-AMP@HA, was designed for synergistic anti-radiation therapy. Fe3+ and Ag+ ions were incorporated into the UiO-67 MOF scaffold, endowing the nanozyme with pH-responsive dual enzymatic activity. Under acidic inflammatory conditions, the strong peroxidase (POD)-like activity generates bactericidal hydroxyl radicals (·), while in neutral healing conditions, superoxide dismutase (SOD)-like activity absorbs reactive oxygen species (ROS) to alleviate tissue damage. Additionally, the surface functionalization of the antibacterial peptide LL-37 enhances the destruction of bacterial membranes, and the HA coating improves biocompatibility and stability. The resulting nano-composite material exhibits potent broad-spectrum antibacterial activity and effectively eliminates bacterial biofilms in vitro. Moreover, MOF-FeAg-AMP@HA promotes tissue repair by stimulating endothelial cell migration and angiogenesis. In vivo, using a rat AP model, the nano-composite material blocks the NF-κB/HIF-1α/NLRP3 signaling axis, inhibits alveolar bone resorption, and thereby suppresses the tremor of the parasite. At the same time, it induces macrophages to polarize towards the anti-inflammatory M2 phenotype, thereby reprogramming the microenvironment for bone regeneration. This microenvironment-responsive platform integrates infection control, immune regulation, and tissue regeneration, providing a promising strategy for the precise treatment of AP. This research was published in ACS Nano under the title "Engineering Smart Bimetallic Ionic-Site MOF Nanozyme Nanocomposites for Microenvironment-Responsive Dynamic Therapy of Periapical Periodontitis".

DOI: 10.1021/acsnano.5c18916