Biofilms are surface-attached bacterial communities embedded within an extracellular matrix that create localized and protected microenvironments. Acidogenic oral biofilms can demineralize the enamel-apatite on teeth, causing dental caries (tooth decay). Current antimicrobials have low efficacy and do not target the protective matrix and acidic pH within the biofilm. Recently, catalytic nanoparticles were shown to disrupt biofilms but lacked a stabilizing coating required for clinical applications. Here, we report dextran-coated iron oxide nanoparticles termed nanozymes (Dex-NZM) that display strong catalytic (peroxidase-like) activity at acidic pH values, target biofilms with high specificity, and prevent severe caries without impacting surrounding oral tissues in vivo. Nanoparticle formulations were synthesized with dextran coatings (molecular weights from 1.5 to 40 kDa were used), and their catalytic performance and bioactivity were assessed. We found that 10 kDa dextran coating provided maximal catalytic activity, biofilm uptake, and antibiofilm properties. Mechanistic studies indicated that iron oxide cores are the source of catalytic activity, whereas dextran on the nanoparticle surface provided stability without blocking catalysis. Dextran-coating facilitated NZM incorporation into exopolysaccharides (EPS) structure and binding within biofilms, which activated hydrogen peroxide (H₂O₂) for localized bacterial killing and EPS-matrix breakdown. Surprisingly, dextran coating enhanced selectivity toward biofilms while avoiding binding to gingival cells. Furthermore, Dex-NZM/H₂O₂ treatment significantly reduced the onset and severity of caries lesions (vs control or either Dex-NZM or H₂O₂ alone) without adverse effects on gingival tissues or oral microbiota diversity in vivo. Therefore, dextran-coated nanozymes have potential as an alternative treatment to control tooth decay and possibly other biofilm-associated diseases.

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