Stimuli-responsive graphdiyne-silver nanozymes for catalytic ion therapy of dental caries through targeted biofilms removal and remineralization

Clinical mechanical decontamination and irrigants are not consistently effective in preventing intractable biofilm-induced dental caries, especially when biofilms have caused demineralization. Constructing stimuli-responsive nanocatalysts with improved catalytic activity for plaque biofilm removal and remineralization enhancement remains challenging. Herein, a coordination-reduction strategy driven by L-cysteine and graphdiyne (GDY) is employed to anchor low-dose Ag nanoparticles/Ag+ to GDY nanosheets to obtain GDY/L-cys/Ag (GLA) nanozymes. Subsequently, biomimetic approach is used to encapsulate GLA into a GS ointment composed of gelatin methacryloyl and sodium alginate to form biodegradable and adhesive GLA/GS. GLA demonstrates acidic plaque biofilm-activated peroxidase-like activity, surpassing affinity toward H2O2 than natural horseradish peroxidase, effectively catalyzing low-dose H2O2 into highly toxic hydroxyl radicals (•OH). This catalytic activity simultaneously enhances Ag+ release triggered by acidic plaque biofilms, generating additional reactive oxygen species that can suppress plaque biofilms on ex vivo human teeth by the synergistic effect of catalysis and released ions. Importantly, GLA/GS serves as template nucleation sites crosslinked to rich Ca2+, thereby attracting PO43- from saliva, prompting growth into hydroxyapatite on tooth enamel, facilitating rapid remineralization. Due to the safe nanocatalytic ion therapy, in an in vivo rodent model, GLA/GS + H2O2 effectively prevents dental caries without influencing surrounding oral tissues.