Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention
Author:
Huang Yue1, Liu Yuan2ORCID, Pandey Nil1, Shah Shrey1, Simon-Soro Aurea1, Hsu Jessica1ORCID, Ren Zhi1ORCID, Xiang Zhenting1, Kim Dongyeop3ORCID, Ito Tatsuro2, Oh Min Jun1ORCID, Buckley Christine4, Alawi Faizan5, Li Yong2, Smeets Paul6ORCID, Boyer Sarah6, Zhao Xingchen6, Joester Derk6ORCID, Zero Domenick5ORCID, Cormode David1, Koo Hyun1ORCID
Affiliation:
1. University of Pennsylvania 2. Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA 3. Jeonbuk National University 4. Indiana University 5. Department of Cariology, Operative Dentistry and Dental Public Health, Oral Health Research Institute, Indiana University School of Dentistry, Indianapolis, USA 6. Northwestern University
Abstract
Abstract
Dental caries (tooth decay) is the most prevalent human disease caused by oral biofilms, affecting nearly half of the global population despite increased use of fluoride, the mainstay anticaries (tooth-enamel protective) agent. Recently, an FDA-approved iron oxide nanozyme formulation (ferumoxytol, Fer) has been shown to disrupt caries-causing biofilms with high specificity via catalytic activation of hydrogen peroxide, but it is incapable of interfering with enamel acid demineralization. Here, we find notable synergy when Fer is combined with stannous fluoride (SnF2), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, our data show that SnF2 enhances the catalytic activity of Fer, significantly increasing reactive oxygen species (ROS) generation and antibiofilm activity. We discover that the stability of SnF2 (unstable in water) is markedly enhanced when mixed with Fer in aqueous solutions without any additives. Further analyses reveal that Sn2+ is bound by carboxylate groups in the carboxymethyl-dextran coating of Fer, thus stabilizing SnF2 and boosting the catalytic activity. Notably, Fer in combination with SnF2 is exceptionally effective in controlling dental caries in vivo, preventing enamel demineralization and cavitation altogether without adverse effects on the host tissues or causing changes in the oral microbiome diversity. The efficacy of SnF2 is also enhanced when combined with Fer, showing comparable therapeutic effects at four times lower fluoride concentration. Enamel ultrastructure examination shows that fluoride, iron, and tin are detected in the outer layers of the enamel forming a polyion-rich film, indicating co-delivery onto the tooth surface. Overall, our results reveal a unique therapeutic synergism using approved agents that target complementary biological and physicochemical traits, while providing facile SnF2 stabilization, to prevent a widespread oral disease more effectively with reduced fluoride exposure.
Publisher
Research Square Platform LLC
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