Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity

Yuan Liu, Pratap C. Naha, Geelsu Hwang, Dongyeop Kim, Yue Huang, Aurea Simon-Soro, Hoi-In Jung, Zhi Ren, Yong Li, Sarah Gubara, Faizan Alawi, Domenick Zero, Anderson T. Hara, David P. Cormode and Hyun Koo ()
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Yuan Liu: University of Pennsylvania
Pratap C. Naha: University of Pennsylvania
Geelsu Hwang: University of Pennsylvania
Dongyeop Kim: University of Pennsylvania
Yue Huang: University of Pennsylvania
Aurea Simon-Soro: University of Pennsylvania
Hoi-In Jung: University of Pennsylvania
Zhi Ren: University of Pennsylvania
Yong Li: University of Pennsylvania
Sarah Gubara: University of Pennsylvania
Faizan Alawi: University of Pennsylvania
Domenick Zero: Indiana University School of Dentistry
Anderson T. Hara: Indiana University School of Dentistry
David P. Cormode: University of Pennsylvania
Hyun Koo: University of Pennsylvania

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Ferumoxytol is a nanoparticle formulation approved by the U.S. Food and Drug Administration for systemic use to treat iron deficiency. Here, we show that, in addition, ferumoxytol disrupts intractable oral biofilms and prevents tooth decay (dental caries) via intrinsic peroxidase-like activity. Ferumoxytol binds within the biofilm ultrastructure and generates free radicals from hydrogen peroxide (H2O2), causing in situ bacterial death via cell membrane disruption and extracellular polymeric substances matrix degradation. In combination with low concentrations of H2O2, ferumoxytol inhibits biofilm accumulation on natural teeth in a human-derived ex vivo biofilm model, and prevents acid damage of the mineralized tissue. Topical oral treatment with ferumoxytol and H2O2 suppresses the development of dental caries in vivo, preventing the onset of severe tooth decay (cavities) in a rodent model of the disease. Microbiome and histological analyses show no adverse effects on oral microbiota diversity, and gingival and mucosal tissues. Our results reveal a new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease.

Date: 2018
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DOI: 10.1038/s41467-018-05342-x

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