PRJNA438685
Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity
Ferumoxytol is an iron oxide nanoparticle formulation approved by the Food and Drug Administration (FDA) for systemic use to treat iron deficiency. Here, we show that ferumoxytol used as topical agent can effectively disrupt intractable oral biofilms via intrinsic peroxidase-like activity and exhibit a potent therapeutic effect against dental caries (tooth decay) in vivo. Time-lapsed studies reveal that ferumoxytol nanoparticles rapidly catalyze hydrogen peroxide (H2O2) despite their passivating coating, for simultaneous bacterial killing and exopolysaccharides breakdown. The nanoparticles bind within the biofilm ultrastructure, causing bacterial membrane damage and polymer matrix degradation in situ upon exposure to low concentrations of H2O2. Using a human-derived ex vivo biofilm model, ferumoxytol-mediated H2O2 catalysis inhibited biofilm accumulation on natural teeth and prevented enamel surface damage as determined via surface topography and microradiography analyses. In vivo, topical oral treatment with ferumoxytol and H2O2 suppressed the development of dental caries, preventing the onset of tooth cavitation altogether in a rodent model of the disease. In addition, microbiome and histological analyses showed no adverse effects on oral microbiota diversity, while sparing normal gingival and mucosal tissues. Our results reveal a potential new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease.