نبذة مختصرة : Abstract Background Silver nanoparticles (AgNPs) have antibacterial properties with potential applications in managing dental caries. Functionalization with fluoride may further enhance AgNPs’ antibacterial efficacy. This study evaluated the impact of fluoridated AgNPs coated with various surface moieties on their safety profile and antibacterial effects against cariogenic bacteria as a potential anti-cariogenic treatment. Methods AgNP synthesis followed citrate and gallic acid reduction methods with polyethylene glycol (PEG) and polyvinylpyrrolidone coating. Functionalizing AgNPs with sodium fluoride (NaF) proceeded. Testing the safety of synthesized compounds was done on human gingival fibroblasts and oral epithelial cells. Meanwhile, minimum inhibitory concentration (MIC) determination against Streptococcus mutans was executed to verify antibacterial activity. Results Gallic-reduced AgNPs revealed higher yielding capacity than citrate-AgNPs. Cytologically, PEGylation reinforced citrate-AgNPs stability and improved IC50 range up to ∼ 4.2 × 1016 µg/mL and 64.3 µg/mL on fibroblastic and epithelial lineages. PEGylated AgNPs counteracted the cytotoxicity of free NaF with antagonistic combinational effect of NaF@PEG gallic-AgNPs on gingival fibroblasts. Microbiologically, AgNPs recorded an enhanced antimicrobial activity of ∼ 5.3 ± 2.3 µg/mL averaged MIC against Streptococcus mutans. Furthermore, fluoridation of PEG gallic-AgNPs depicted an additive antimicrobial propensity. Conclusions This dual action nanoplatform successfully integrates fluoride and silver components, reducing fluoride concentrations to safety range while maximizing silver’s antibacterial properties. Engineered NaF@PEGylated nanosilver formulation represents promising anti-cariogenic strategy that optimizes therapeutic efficacy while maintaining biological safety.
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