PROJECT SUMMARY/ABSTRACT The problem: With an aging population, challenges to maintain good oral health are set to increase worldwide. Systemic complications (high blood pressure, diabetes, neurodegenerative disorders) add to local factors, such as the exposure of the more susceptible root surfaces and the use of medications that cause hyposalivation. Collectively, these factors increase caries rates, especially root caries, and reduce the oral health and quality of life of older adults. As oral and general health are indivisible, poor oral health outcomes in older individuals are associated with increased frailty and mortality. Challenges to overcome the increased rate of root caries in older adults include the lack of a specific approach for root caries control, the standard of care being the prescription of high fluoride toothpastes. These toothpastes have modest clinical effectiveness, since the retention of fluoride in the biofilm is not proportionally enhanced as the fluoride concentration in the product increases. Although fluoride has been the most effective agent for caries prevention for several decades, surprisingly, no innovations to improve its anticaries efficacy have been made. Hypothesis: We devised a new therapy able to enhance the anticaries effect of fluoride, while maintaining its dose and safety profile. In pilot studies, we observed that this therapy, involving the use of fluoride nanoparticles, increase by approximately 100-fold the penetration and retention of fluoride in cariogenic biofilms, and exhibit an improved fluoride- releasing profile. Thus, we hypothesize that the positively charged nanoparticles will penetrate the cariogenic biofilm, bind to negatively charged biofilm components, and release fluoride at levels high enough to improve the physicochemical effect of fluoride (needed for the control of root caries) as well as inhibit acid production by the biofilm (reducing the predominance of acid-producing species, i.e. biofilm dysbiosis). This hypothesis will be tested in the following specific aims: S.A.#1: Define the mechanisms of interaction between the therapy components and dental biofilm; S.A.#2: Determine the effects of the therapy on root dentin demineralization; S.A.#3: Establish the efficacy and safety of the therapy for caries control using in vivo rodent caries models. Significance: Upon successful completion of this project, we will understand the preventive potential of a new anticaries approach to reduce the cariogenicity of dental biofilm and control root caries. This work has the potential to exert a long-lasting impact on the control of rampant caries progression in high caries-risk groups and improve the health and quality of life of older adults suffering from hyposalivation.