Dental Adhesive Peptides Nanonets as Multifunctional Therapy for Caries

Dental caries poses significant therapeutic challenges due to resilient biofilms and uncontrolled demineralization. To address these challenges, by leveraging the broad antimicrobial activity and strong phosphate-binding capability of arginine peptides, we developed dental adhesive nanonets to effectively capture and kill S. mutans strain for caries management. FmocFFRRR was selected from a two-round structural screenings, and was co-assembled with sodium monofluorophosphate (MFP) to construct multifunctional nanonets (F@MFP). Specifically, F@MFP nanonets adhere robustly to tooth enamel, capture S. mutans via electrostatic interactions and kill S. mutans bydisrupting bacterial membrane integrity, inducing oxidative stress, and suppressing metabolic activities. F@MFP nanonets not only inhibit biofilm formation but also effectively dismantle mature biofilms by downregulating biofilm-associated virulence genes. Furthermore, F@MFP nanonets also serve as a fluoride reservoir to inhibit demineralization and promote enamel regeneration. In vivo experiments reveal that F@MFP exhibits superior caries-inhibiting efficacy. This multifunctional platform integrates dental adhesion, a capture-and-kill antibacterial mechanism, anti-biofilm properties, and enamel repair capacity, offering a novel paradigm for targeted caries therapy.