# Biofilm Elimination and Caries Prevention using Multifunctional Nanocatalysts

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $79,412

## Abstract

ABSTRACT
Dental caries remains an unresolved disease affecting more than 2.3 billion people worldwide. It disproportionally
afflicts impoverished families and medically compromised populations, including those with comorbidities such
as iron-deficiency anemia. Current approaches are insufficient for susceptible populations, where biofilms rapidly
accumulate under sugar-rich diets and poor oral hygiene leading to onset of dental caries that cannot be
effectively controlled, requiring new antibiofilm approaches. Fluoride, the anticaries mainstay, promotes
remineralization and reduces tooth enamel demineralization, but is ineffective against biofilms. Conversely,
current antimicrobials are restricted to broad-spectrum agents that can disrupt oral microbiota diversity while
lacking efficacy against dental caries. Thus, an alternative approach is needed to address the limitations of
current treatments and help control dental caries under pathogenic conditions. A major challenge is the rapid
establishment of intractable microbial biofilms in susceptible individuals. In cariogenic biofilms, bacterial cells are
enmeshed in an exopolysaccharides (EPS) matrix, forming highly organized and protected biostructures that
create localized acidic microenvironments. These low pH niches further induce cariogenic bacteria growth,
ensuring biofilm build-up and acid dissolution of tooth enamel. To overcome these challenges, new antibiofilm
strategies are needed to precisely target the biofilm properties and the acidogenic environment, and at the
same time, prevent enamel acid-demineralization. In the previous funding period, we studied the potential of
catalytic (peroxidase mimics) iron oxide nanoparticles (IONP) for controlled, acidic pH-dependent activation of
hydrogen peroxide as a novel antibiofilm and anticaries treatment. We found that this approach potently
disrupted cariogenic biofilms and blocked apatite acid dissolution, significantly reducing dental caries in rodent
models. Furthermore, we discovered that coating IONP with dextran enhanced targeting specificity by improving
retention and incorporation into biofilm, while deterring binding to cellular and soft-tissue surfaces, providing a
selective biofilm-targeting approach. In vivo studies revealed that dextran coated IONP were highly effective
against caries development without affecting gingival/mucosal tissues and oral microbiome diversity, confirming
therapeutic precision. These findings were further confirmed using ferumoxytol, an FDA-approved IONP used
for iron deficiency therapy, that has similar size and dextran-coating to those made in-house. Recently, we
received an IND exemption for repurposing ferumoxytol for topical treatment in human in situ model studies. This
proposal is to further develop and understand catalytic nanoparticle technology for effective treatment of
cariogenic biofilms and prevention of dental caries using the ferumoxytol FDA approved IONP as a nanocarrier.

## Key facts

- **NIH application ID:** 10738950
- **Project number:** 3R01DE025848-07S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Hyun Koo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $79,412
- **Award type:** 3
- **Project period:** 2016-12-09 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10738950

## Citation

> US National Institutes of Health, RePORTER application 10738950, Biofilm Elimination and Caries Prevention using Multifunctional Nanocatalysts (3R01DE025848-07S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10738950. Licensed CC0.

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