Modified casein-stabilized amorphous calcium phosphate nanoparticles prevent dental caries by inhibiting the growth of Streptococcus mutans and promoting the remineralization of tooth enamel

Dental caries, a prevalent oral disease, is caused by acid- producing plaque microorganisms-notably Streptococcus mutans ( S. mutans )-which drive enamel demineralization. Current prevention strategies, such as fluoride and chlorhexidine, primarily target planktonic bacteria but exhibit limited efficacy against biofilms and neglect enamel remineralization, thereby reducing their therapeutic efficacy. To address these limitations, we developed dual-functional nanoparticles (AXCP NPs) that can eradicate S. mutans biofilm and promote enamel remineralization. The amphiphilic polymer Arg-XOS-CPP (AXC) was synthesized by covalently conjugating oligosaccharide carbonyl groups to the amino residues of L-arginine and casein. Self-assembly of AXC with calcium and phosphate ions yielded hybrid nanoparticles (AXCP NPs). Experimental results indicated that AXCP NPs had no effect on the viability of HaCaT cells. Under acidic conditions, protonation of arginine triggered a surface charge reversal from negative to positive, enabling targeted binding to negatively charged biofilms. As expected, AXCP NPs exhibited potent anti- S. mutans activity (MIC: 640   μg/mL) and remarkable biofilm eradication efficacy (>80% clearance). In vitro release and remineralization assays demonstrated that AXCP NPs continuously released calcium and phosphorus ions, regulating the mineralization process and effectively restoring enamel functionality. Furthermore, in mice caries model, localized application of AXCP NPs significantly suppressed biofilm accumulation on tooth surface and restored mineral density in demineralized enamel, inhibiting caries progression.