Near-infrared light-responsive copper-cerium bimetallic oxide nanozyme with antibacterial and antioxidant abilities for periodontitis therapy

Abstract

Periodontitis, a chronic inflammatory disease of the supporting tissue around teeth, is triggered by periodontal pathogens. Clinical treatments face the problem of bacterial resistance and most therapies focus on a single function, lacking the multifunctional treatment of antibacterial, antioxidant, anti-inflammatory, and osteogenic properties. In our study, we developed a copper-cerium bimetallic oxide (CuCeO_x) nanozyme with near-infrared (NIR) light responsiveness for the periodontitis therapy. Under the excitation of 808 nm NIR light, CuCeO_x displayed excellent photodynamic and photothermal activities, efficiently generating reactive oxygen species (ROS) and heat. After the treatment of the CuCeO_x/NIR system, the inhibition rate of Porphyromonas gingivalis (P. gingivalis), the main periodontitis pathogen, reached 98.69 ± 0.23 % in vitro. Without the NIR light irradiation, CuCeO_x, acting as a nanozyme, exhibited enzyme-like activity in scavenging ROS, effectively alleviating the cellular oxidative stress. Furthermore, CuCeO_x significantly mitigated the cellular inflammatory response induced by lipopolysaccharide (LPS) and promoted osteogenesis under the oxidative stress condition. Notably, the CuCeO_x exhibited excellent blood compatibility (hemolysis < 5 %). The efficacy of the CuCeO_x/NIR system in vivo was also investigated. H&E staining results demonstrated a significant reduction in periodontal tissue inflammation following treatment. Micro-CT analysis revealed that CuCeO_x effectively inhibited the alveolar bone loss. Additionally, we found CuCeO_x regulated the Nrf2/HO-1 signaling pathway both in vitro and in vivo. In conclusion, the multifunctional nanomaterial CuCeO_x provides a promising strategy for the treatment of periodontitis.