Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention

Abstract

Dental caries is the most common human disease caused by oral biofilms despite the widespread use of fluoride as the primary anticaries agent. Recently, an FDA-approved iron oxide nanoparticle (ferumoxytol, Fer) has shown to kill and degrade caries-causing biofilms through catalytic activation of hydrogen peroxide. However, Fer cannot interfere with enamel acid demineralization. Here, we show notable synergy when Fer is combined with stannous fluoride (SnF2), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, we discover that the stability of SnF2 is enhanced when mixed with Fer in aqueous solutions while increasing catalytic activity of Fer without any additives. Notably, Fer in combination with SnF2 is exceptionally effective in controlling dental caries in vivo, even at four times lower concentrations, without adverse effects on host tissues or oral microbiome. Our results reveal a potent therapeutic synergism using approved agents while providing facile SnF2 stabilization, to prevent a widespread oral disease with reduced fluoride exposure.

Nonradical Surface Chemistry Mechanisms for Catalytic Nanoparticles

“…The free radical mechanism is usually accepted because of the following experimental evidence: the strong ·OH signals can be detected after nanoparticles are added to the H 2 O 2 solution by electron spin resonance, fluorescent probe, and other methods for detecting ·OH (Figure a), suggesting that these particles can promote the formation of ·OH by reacting with H 2 O 2 . Because there is a large amount of H 2 O 2 in cells, nanoparticles can promote formation of free radicals by converting H 2 O 2 to ·OH to induce their medical functions. − These techniques have also been applied to detect other radical signals, such as O 2•– and 1 O 2 , , seemingly sufficient to support the free radical mechanism.…”

The potential use of nanozymes as an antibacterial agents in oral infection, periodontitis, and peri-implantitis

“…Notably, even at four times lower concentrations, the combination of SnF 2 and Fer shows significant effectiveness against dental caries in vivo without adversely affecting the oral microbiota or host tissues. The results of this study show that authorized medications and SnF 2 stabilization have a solid therapeutic synergy that may be used to lower fluoride exposure and prevent widespread oral illnesses [ 78 ].…”

“…The potential for utilizing SnF 2 and Fer to treat anemia and tooth decay, two of the most significant global health issues, presents a viable opportunity to incorporate combination therapy into clinical trials to prevent dental caries in high-risk patients with iron-deficiency anemia. The findings of the researchers demonstrate a powerful therapeutic synergy between approved agents and SnF 2 stabilization, which can be used to reduce fluoride exposure and prevent a common oral disease [ 78 ].Low catalytic activity and an unknown catalytic mechanism Although natural enzymes have been incorporated into toothpaste for therapeutic purposes, they remain more effective than NZs. They can whiten teeth as well as reduce dental calculus and plaque due to their potent catalytic activity, transparent catalytic mechanism, and superior biological safety [ 157 ].…”

The Story of Ferumoxytol: Synthesis Production, Current Clinical Applications, and Therapeutic Potential

“…In addition, the recent study conducted by Hyun Koo et al. [ 84 ] has revealed that the combined utilization of ferumoxytol and stannous fluoride can effectively inhibit biofilm accumulation and enamel damage. Ferumoxytol enhances the stability of stannous fluoride in aqueous solution, while the addition of stannous fluoride stimulates ferumoxytol to exhibit enhanced catalytic activity.…”