Microenvironment-responsive NIR-IIb multifunctional nanozyme platform for bacterial imaging and specialized anti-anaerobic bacteria periodontal therapy

Periodontitis is a chronic inflammatory disease caused by plaque. In order to remove pathogens and promote tissue repair, the following steps need to be taken simultaneously: localizing the diseased area, improving the anaerobic microenvironment, as well as addressing the anti-inflammatory and osteogenic needs. This study aims to address these issues by developing a responsive near-infrared-IIb nanozyme system (DMUP), assembled from lanthanide-doped down-converted nanoparticles and multi-enzymatically active nanozyme. DMUP binds to bacterial membranes via the bacterial targeting peptide ubiquicidin_29-41 (UBI_29-41). Upon responding to the inflammatory microenvironment, it releases manganese (Mn) nanozyme and paeonol (Pae), and localized infected areas by fluorescent bacterial imaging in the near-infrared IIb (NIR-IIb) region. In particular, the released Mn nanozyme reacts with hydrogen peroxide in the inflammatory microenvironment to generate oxygen (O₂) in situ, thereby improving the anoxic environment to inhibit anaerobic bacteria. On the other hand, as a metal oxide nanozyme, Mn nanozyme scavenges reactive oxygen species (ROS) by mimicking the cascade process of superoxide dismutase and catalase. The phenolic antioxidant Pae shifts macrophages from pro-inflammatory (M1-type) to anti-inflammatory (M2-type) through the Akt/mTOR pathway. It can synergize with Mn nanozyme to regulate the inflammatory microenvironment, thereby reducing inflammation, promoting osteogenic genes expression, and accelerating periodontal tissues regeneration.