Near‐infrared light-triggered nitric oxide nanocomposites for photodynamic/photothermal complementary therapy against periodontal biofilm in an animal model

Background: Periodontal disease, an oral disease that initiates with plaque biofilm infection, affects 10% of the global population. Due to the complexity of tooth root anatomy, biofilm resistance and antibiotic resistance, traditional mechanical debridement and antibiotic removal of biofilms are not ideal. Nitric oxide (NO) gas therapy and its multifunctional therapy are effective methods to clear biofilms. However, large and controlled delivery of NO gas molecules is currently a great challenge. Methods: The core-shell structure of Ag₂S@ZIF-90/Arg/ICG was developed and characterized in detail. The ability of Ag₂S@ZIF-90/Arg/ICG to produce heat, ROS and NO under 808 nm NIR excitation was detected by an infrared thermal camera, probes and Griess assay. In vitro anti-biofilm effects were evaluated by CFU, Dead/Live staining and MTT assays. Hematoxylin-eosin staining, Masson staining and immunofluorescence staining were used to analyze the therapeutic effects in vivo. Results: Antibacterial photothermal therapy (aPTT) and antibacterial photodynamic therapy (aPDT) could be excited by 808 nm NIR light, and the produced heat and ROS further triggered the release of NO gas molecules simultaneously. The antibiofilm effect had a 4-log reduction in vitro. The produced NO caused biofilm dispersion through the degradation of the c-di-AMP pathway and improved biofilm eradication performance. In addition, Ag₂S@ZIF-90/Arg/ICG had the best therapeutic effect on periodontitis and NIR II imaging ability in vivo. Conclusions: We successfully prepared a novel nanocomposite with NO synergistic aPTT and aPDT. It had an outstanding therapeutic effect in treating deep tissue biofilm infection. This study not only enriches the research on compound therapy with NO gas therapy but also provides a new solution for other biofilm infection diseases.