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; Hyun Koo

doi:10.1038/s41467-023-41687-8

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^*Hyun Koo^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English (US)
Article number	6087
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-41687-8
State	Published - Dec 2023

Funding

This work was supported by the NIH grant R01-DE025848 to H.K. This work made use of the EPIC facility of Northwestern University\u2019s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern\u2019s MRSEC program (NSF DMR-1720139). Research reported in this publication was supported in part by instrumentation provided by the Office of the Director, National Institutes of Health, under Award Number S10OD026871. S.B. was in part supported by the National Institutes of Health\u2019s National Center for Advancing Translational Sciences, Grant Number TL1TR001423. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Z.R. is supported by the National Institute of Dental and Craniofacial Research Postdoctoral Training Program under Award R90DE031532. We would also like to thank Liam Spillane from Gatan, Inc. for aid with the STEM-EELS acquisition. A portion of the schematic diagram in Fig.\u00A01e was generated using BioRender.com (Agreement number: UO25QG4RN3). This work was supported by the NIH grant R01-DE025848 to H.K. This work made use of the EPIC facility of Northwestern University\u2019s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern\u2019s MRSEC program (NSF DMR-1720139). Research reported in this publication was supported in part by instrumentation provided by the Office of the Director, National Institutes of Health, under Award Number S10OD026871. S.B. was in part supported by the National Institutes of Health\u2019s National Center for Advancing Translational Sciences, Grant Number TL1TR001423. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Z.R. is supported by the National Institute of Dental and Craniofacial Research Postdoctoral Training Program under Award R90DE031532. We would also like to thank Liam Spillane from Gatan, Inc. for aid with the STEM-EELS acquisition. A portion of the schematic diagram in Fig. was generated using BioRender.com (Agreement number: UO25QG4RN3).

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Huang, Y., Liu, Y., Pandey, N. K., Shah, S., Simon-Soro, A., Hsu, J. C., Ren, Z., Xiang, Z., Kim, D., Ito, T., Oh, M. J., Buckley, C., Alawi, F., Li, Y., Smeets, P. J. M., Boyer, S., Zhao, X., Joester, D., Zero, D. T., ... Koo, H. (2023). Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention. Nature communications, 14(1), Article 6087. https://doi.org/10.1038/s41467-023-41687-8

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title = "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.",

author = "Yue Huang and Yuan Liu and Pandey, {Nil Kanatha} and Shrey Shah and Aurea Simon-Soro and Hsu, {Jessica C.} and Zhi Ren and Zhenting Xiang and Dongyeop Kim and Tatsuro Ito and Oh, {Min Jun} and Christine Buckley and Faizan Alawi and Yong Li and Smeets, {Paul J.M.} and Sarah Boyer and Xingchen Zhao and Derk Joester and Zero, {Domenick T.} and Cormode, {David P.} and Hyun Koo",

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year = "2023",

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doi = "10.1038/s41467-023-41687-8",

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Huang, Y, Liu, Y, Pandey, NK, Shah, S, Simon-Soro, A, Hsu, JC, Ren, Z, Xiang, Z, Kim, D, Ito, T, Oh, MJ, Buckley, C, Alawi, F, Li, Y, Smeets, PJM, Boyer, S, Zhao, X, Joester, D, Zero, DT, Cormode, DP & Koo, H 2023, 'Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention', Nature communications, vol. 14, no. 1, 6087. https://doi.org/10.1038/s41467-023-41687-8

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T1 - Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention

AU - Huang, Yue

AU - Liu, Yuan

AU - Pandey, Nil Kanatha

AU - Shah, Shrey

AU - Simon-Soro, Aurea

AU - Hsu, Jessica C.

AU - Ren, Zhi

AU - Xiang, Zhenting

AU - Kim, Dongyeop

AU - Ito, Tatsuro

AU - Oh, Min Jun

AU - Buckley, Christine

AU - Alawi, Faizan

AU - Li, Yong

AU - Smeets, Paul J.M.

AU - Boyer, Sarah

AU - Zhao, Xingchen

AU - Joester, Derk

AU - Zero, Domenick T.

AU - Cormode, David P.

AU - Koo, Hyun

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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

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