<i>Porphyromonas gingivalis</i>-Derived Immunologic Nanozymes as Smart Microenvironment-Adaptive Regulators for Programmed Cascade Treatment of Oral Mucosal Infection.

Abstract

Smart reactive oxygen species (ROS) regulation systems associated with the dynamic treatment of all infected wounds, including oral ones, usually involve the generation of ROS to kill pathogens and the reduction of ROS levels to promote tissue repair, which seems impossible to achieve simultaneously. Meanwhile, remodeling the immune microenvironment is also crucial for oral wound healing. Herein, a microenvironment-adaptive immunologic nanozyme based on <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>)-derived nanodots (P-dots) is developed for the programmed cascade therapy of oral mucosal infection by regulating nanozyme-assisted cascade reactions. Due to the retention of active Fe-N₄ centers of heme and similar molecular patterns related to <i>P. gingivalis</i>, P-dots prepared via a facile hydrothermal strategy exhibit admirable multienzyme catalytic activity and ideal immunomodulation function. More importantly, P-dots enable dynamic regulation of ROS production and elimination in response to changes in the oral infected wound microenvironment. Specifically, P-dots exhibit peroxidase-like catalytic activity in the early stages of oral mucosal infection, leading to the production of ROS that kill bacteria. After disinfection, P-dots switch to superoxide dismutase-like and catalase-like catalytic behaviors and scavenge unwanted ROS around the wounds. Together, our well-developed P-dots-involved system with high biosafety can serve as an intelligent microenvironment-adaptive approach for the dynamic, whole-stage therapy of oral mucosal infection through accurate ROS regulation.