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

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.

Applications of nano-materials in diverse dentistry regimes

“…Researchers have found a novel bio-medical application for ferumoxytol as a topical therapy for the common and prevalent bio-lm, which results in oral diseases. 108 A bio-nanocomposite of Carboxymethyl Starch (CMS)-Chitosan (CS)-Montmorillonite (MMT) has been designed to deliver Curcumin (Jahanizadeh et al). They used ionic gelation technique and examined its anti-biolm activities versus Streptococcus mutans.…”

Nanoparticles for the Treatment of Oral Biofilms: Current State, Mechanisms, Influencing Factors, and Prospects

“…Nanoparticles have good designability compared with traditional antibiotics, and specifically designed nanoparticles can prevent and treat oral biofilm infectious diseases through microecological modulation of the oral cavity flora and biofilms . The development of selective nanoparticles that regulate the microecological balance of oral pathogenic biofilms has become an important area of research.…”

“…Controlling the key metabolic environmental factors that induce the pathogenic transformation of multicell community, instead of blindly killing opportunistic pathogens, will more effectively maintain the original microecological balance. The most promising method for achieving this is surface modification of nanoparticles ( Figure ). Study has shown that highly specific targeting of the acidic pH in oral biofilms can be obtained by treating ferric oxide nanoparticles with a dextran coating.…”

“…Insets: negative stain TEM of ferumoxytol (scale bar: 50 and 10 nm for close up image) and hydrodynamic diameter measurements. Adapted under the terms of the Creative Commons CC BY license . Copyright 2018, the Author(s).…”

Applications and Perspectives of Cascade Reactions in Bacterial Infection Control

“…ROS are sometimes called "the sword of nanotechnology, " and taking lessons from cancer therapy, several methods have become available to generate ROS (Sun et al, 2014;Liu X. et al, 2019). ROS produced by different types of nanoparticles in combination with the addition of external H 2 O 2 (Gao et al, 2016;Liu et al, 2018;Naha et al, 2019) has been shown to be effective in biofilm eradication. However, the use of cascade reactions to counter bacterial infections through ROS production using endogenously present substrate, i.e., without addition of external H 2 O 2 , has not yet been extensively considered.…”