Lysine aggregates‐based nanostructured antimicrobial peptides for cariogenic biofilm microenvironment‐activated caries treatment

Abstract Dental caries is one of the most prevalent and costly biofilm‐induced oral diseases that causes the deterioration of the mineralized tooth tissue. Traditional antimicrobial agents like antibiotics and antimicrobial peptides (AMPs) struggle to effectively eradicate bacteria in biofilms without eliciting resistance. Herein, we demonstrate the construction of FeOOH@Fe‐Lysine@Au nanostructured AMPs (nAMPs) distinguished by their AMP‐like antibacterial activity and self‐producing reactive oxygen species (ROS) capacity for caries treatment. On the one hand, FeOOH@Fe‐Lysine@Au nAMPs can catalyze glucose oxidation to generate ROS within the cariogenic biofilm microenvironment, resulting in the disintegration of the extracellular polymeric substance matrix and the exposure of bacteria. On the other hand, FeOOH@Fe‐Lysine@Au nAMPs can attach to bacterial surfaces via electrostatic attractions, proceeding to damage membranes, disrupt metabolic pathways, and inhibit protein synthesis through the aggregated lysine and the generated ROS. Based on this antibacterial mechanism, FeOOH@Fe‐Lysine@Au nAMPs can effectively eradicate Streptococcus mutans and its associated biofilm, significantly impeding the progression of dental caries. Given the straightforward and cost‐efficient preparation of FeOOH@Fe‐Lysine@Au nAMPs compared to AMPs that require specific sequences, and their minimal adverse impacts on gingival/palatal tissues, major organs, and oral/gut microbiomes, our research may promote the development of novel therapeutic agents in dental health maintenance.