pH-Responsive Hybrid Nanoparticles for Imaging Spatiotemporal pH Changes in Biofilm-Dentin Microenvironments

Engineering highly sensitive nanomaterials to monitor spatiotemporal pH changes has rather broad applications in studying various biological systems. Intraoral/biofilm–tooth pH is the single parameter that has demonstrated accurate assessment of dental caries risk, reflecting the summative integrated outcome of the complicated interactions between three etiological factors, namely, microorganisms/biofilm, diet/carbohydrates, and tooth/saliva/host. However, there is little to no technology/system capable of accurately probing simultaneously both the micro-pH profiles in dentin tissues and acidogenic oral biofilms and examining the pathophysiologic acid attacks with high spatial/temporal resolution. Therefore, a highly sensitive pH-responsive hybrid nanoparticle (pH-NP) is developed and coupled with an ex vivo tooth–biofilm caries model to simulate and study the key cariogenic determinants/steps. The pH-NP emits two distinct fluorescences with mutually inversely proportional intensities that vary accordingly to the proximity pH and with a ratiometric output sensitivity of 13.4-fold across a broad clinically relevant pH range of 3.0–8.0. Using [H⁺], in addition to pH, to calculate the “area-under-curve” corroborates the “minimum-pH” in semiquantifying the demineralizing potential in each biofilm-dentin zones/depth. The data mechanistically elucidates a two-pronged cariogenic effect of a popular-acidic-sweet-drink, in inundating the biofilm/tooth-system with H⁺ ions from both the drink and the metabolic byproducts of the biofilm.