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

Yue Huang, Yuan Liu, Nil Kanatha Pandey, Shrey Shah, Aurea Simon-Soro, Jessica C. Hsu, Zhi Ren, Zhenting Xiang, Dongyeop Kim, Tatsuro Ito, Min Jun Oh, Christine Buckley, Faizan Alawi, Yong Li, Paul J. M. Smeets, Sarah Boyer, Xingchen Zhao, Derk Joester, Domenick T. Zero, David P. Cormode () and Hyun Koo ()
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Yue Huang: University of Pennsylvania
Yuan Liu: University of Pennsylvania
Nil Kanatha Pandey: University of Pennsylvania
Shrey Shah: University of Pennsylvania
Aurea Simon-Soro: University of Pennsylvania
Jessica C. Hsu: University of Pennsylvania
Zhi Ren: University of Pennsylvania
Zhenting Xiang: University of Pennsylvania
Dongyeop Kim: University of Pennsylvania
Tatsuro Ito: University of Pennsylvania
Min Jun Oh: University of Pennsylvania
Christine Buckley: Indiana University School of Dentistry
Faizan Alawi: University of Pennsylvania
Yong Li: University of Pennsylvania
Paul J. M. Smeets: Northwestern University
Sarah Boyer: Northwestern University
Xingchen Zhao: Northwestern University
Derk Joester: Northwestern University
Domenick T. Zero: Indiana University School of Dentistry
David P. Cormode: University of Pennsylvania
Hyun Koo: University of Pennsylvania

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41687-8

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