Abstract
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 (O(2)) 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.