Dextranase-loaded pH and near-infrared dual-responsive Cu2O-embedded mesoporous organosilica nanoparticles for biofilm disruption and microecology-friendly caries prevention

Dental caries remains a significant public health challenge due to the persistent presence of cariogenic biofilms. Cuprous oxide nanoparticles (Cu₂O NPs) show promise in inhibiting biofilm formation; however, extracellular polymeric substances (EPS) form a robust barrier that limits nanoparticle penetration and diminishes their anti-caries effectiveness. To address this, we loaded dextranase (DEX) onto Cu₂O-embedded periodic mesoporous organosilica (PMO) nanoparticles (Cu₂O-PMO@DEX/PEG NPs), which integrate enzymatic EPS hydrolysis, pH-triggered release of copper ions, and near-infrared (NIR) photothermal therapy, providing a multifaceted approach to overcome biofilm barriers. Cu₂O-PMO@DEX/PEG NPs exhibited potent activity against S. mutans , achieving a minimum inhibitory concentration (MIC) value of 78.125 μg/mL, corresponding to an effective Cu₂O dose of ~5.4 μg/mL. In a rat caries model, Cu₂O-PMO@DEX/PEG NPs achieved caries-preventive efficacy comparable to chlorhexidine (CHX). The 16S rRNA sequencing showed that the system suppressed pathogenic taxa, preserved commensal flora, without the enrichment of antimicrobial-resistance-associated taxa observed in the CHX group, demonstrating superior microecological compatibility compared with CHX-induced dysbiosis. Biosafety of this system was confirmed by cytotoxicity testing and in vivo histopathological evaluation. This work establishes a strategy to combat cariogenic biofilm barriers and provides a microecology-friendly design foundation for next-generation caries prevention materials.