Guanidination carbon dots combat Streptococcus mutans biofilm through downregulating carbohydrate metabolism to prevent dental caries

Dental caries is one of the most common chronic bacterial infections in humans, primarily caused by Streptococcus mutans ( S. mutans ) and the biofilms formed on tooth surfaces. Efficient and easily implementable preventive strategies for dental caries are still needed. In this study, we synthesized guanidination carbon dots (HG-CDs) bearing guanidine and quaternary ammonium groups via a melting strategy. The HG-CDs, with an average particle size of ∼3 nm and a positive zeta potential of +11.8 mV, exhibited strong binding and deep penetration into S. mutans biofilms, leading to significant inhibition of biofilm growth, with biofilm biomass reduced by approximately 90 %, and inducing bacterial lysis. Transcriptomic and qRT-PCR analyses revealed that HG-CDs markedly downregulated key carbohydrate metabolism genes ( gbpB , the gtf family, and ftf ), thereby blocking exopolysaccharide synthesis and preventing biofilm reconstruction. In ex vivo tooth model, HG-CDs effectively eradicated established biofilms. In vivo , similar to that of CHX treatment, HG-CDs delivered via a mouthwash approach significantly reduced the incidence of early and moderate pit-and-fissure caries in molars, while HG-CDs treatment notably delayed lesion progression. Collectively, HG-CDs integrate efficient antibacterial, antibiofilm, and anticaries capabilities, paving a practical path for developing an advanced oral care formulations and holding significant translational promise for intervening in oral infectious diseases especially for dental caries.