Modulating silver diamine fluoride chemical derivatives by solid-binding peptides

Peptide modulators offer a means to transition from passive dental treatment to actively designing the biological interface with specific responses for efficacy and minimal off-target effects. The oral cavity is exposed to one of the most hostile and dynamic environments in the human body. Targeted delivery of peptide modulators may direct the desired biological outcomes at the interface of dental bioceramic tissues. While noninvasive silver diamine fluoride (SDF) has revolutionized cavity management in early childhood caries, its universal use is limited by its drawbacks including permanent black stain on treated tissues. To mitigate these drawbacks, we investigated the effects of a silver diamine fluoride modulating peptide (SDF-ModP) on silver compound formation and staining outcomes in SDF-treated dentin. Slabs of human dentin tissue were treated with SDF alone or SDF followed by SDF-ModP. Raman micro-spectroscopy and X-ray photoelectron spectroscopy (XPS) were used to identify the silver compounds. The color change was monitored over time using the CIELAB color space. Raman analysis identified silver chloride (AgCl), silver (I) oxide (Ag₂O), and silver (II) oxide (AgO) as the most abundant compounds formed in SDF-treated dentin. XPS deconvolution of the Ag 3d _5/2 region confirmed the coexistence of metallic silver (Ag (0)), Ag (I), and Ag (III) species. SDF-ModP treatment modulated the distribution of these species, reducing both metallic silver and Ag (III) oxide formation, while increasing the proportion of Ag (I) compounds. Over a 7-day monitoring period, time-resolved color analysis revealed that SDF-ModP delayed and reduced overall black staining compared to SDF alone. The peptide modulated silver chemistry by reducing the formation rate of metallic silver chromophores and higher-valence oxides, thereby decreasing dentin discoloration. These findings suggest that SDF-modulating peptides can be used to improve the therapeutic efficacy and esthetic outcomes of SDF therapy. Our approach represents a molecular biomimetic engineering strategy in which specific peptide interactions with metal ions to modulate the biological interface. This strategy could be extended to other metal-based therapeutics, where precise control of metal ion speciation is desired.