Microenvironment‐Driven Fenton Nanoreactor Enabled by Metal‐Phenolic Encapsulation of Calcium Peroxide for Effective Control of Dental Caries

Abstract Caries are one of the most common oral diseases caused by pathogenic bacterial infections, which are widespread and persistently harmful to human health. Using nanoparticles to invade biofilms and produce reactive oxygen species (ROS) in situ is a promising strategy for killing bacteria and disrupting the structure of biofilms. In this work, a biofilm‐targeting Fenton nanoreactor is reported that can generate ROS responsive to the cariogenic microenvironment. The nanoreactor is constructed by metal‐phenolic encapsulation of calcium peroxide (CaO 2 ) followed by modification with a biofilm targeting ligand dextran. Within the cariogenic biofilm, the Fenton nanoreactor is activated by an acidic microenvironment to be decomposed into H 2 O 2 and iron ions, triggering a Fenton‐like reaction to generate ROS that can eliminate the biofilm by breaking down extracellular polymeric substances (EPS) and killing cariogenic bacteria. Meanwhile, the depletion of excess protons in biofilm leads to a reversal of the cariogenic microenvironment. The Fenton nanoreactor can effectively inhibit the biofilm formation of Streptococcus mutans on ex vivo human teeth and is effective in preventing caries meanwhile maintaining the oral microbial diversity in rat caries infection model. This work provides a novel and efficient modality for acid microenvironment‐driven ROS therapy.