# Biofilm Elimination and Caries Prevention using Multifunctional Nanocatalysts

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $608,773

## Abstract

Despite the high prevalence of biofilm-related oral diseases such as dental caries, there are no clinically
effective therapies to disrupt virulent biofilms, resulting in >$40 billion expenditures annually in the US.
Effective control of cariogenic biofilms is notoriously challenging because the bacteria are enmeshed in a
protective extracellular matrix rich in exopolysaccharides (EPS). Furthermore, EPS-enmeshed bacteria create
highly acidic microenvironments that promote acid-dissolution of tooth enamel, leading to the onset of dental
caries. Current antimicrobial agents are incapable of disrupting the EPS matrix or affecting the physico-
chemical aspects of caries and often fail to efficiently kill the microbes within biofilms, resulting in limited
efficacy in vivo. To overcome these remarkable hurdles, we have developed an exciting therapeutic strategy
using biocompatible iron oxide nanoparticles (IO-NP) with catalytic activity and pH-responsive properties that
display both anti-biofilm and anti-caries actions. IO-NP exhibit peroxidase-like activity at acidic pH values that
rapidly activates hydrogen peroxide (H2O2) in situ to simultaneously degrade the protective biofilm EPS-matrix
and kill embedded bacteria with exceptional efficacy (>5-log reduction of cell viability) in 5 minutes. Moreover,
IO-NP also reduce apatite demineralization in acidic conditions. We hypothesize that IO-NP synergizes with
H2O2 to amplify anti-biofilm effects and prevent the onset of dental caries in vivo via nanocatalysis and
enhanced in situ production of antibacterial, EPS-degrading and demineralization-blocking agents at acidic pH.
The significance of this work is to develop a feasible and superior anti-biofilm and caries preventive approach
compared to current chemical modalities. To test our hypothesis, we will optimize the efficacy of IO-NP/H2O2 to
further improve anti-biofilm and demineralizing-blocking activities (Aim 1). We will enhance the catalytic activity
of IO-NP by inclusion of specific metal salts into the nanoparticles, and explore the effects of various dextran-
based coatings to increase IO-NP localization within biofilm structure. Furthermore, we will incorporate
calcium-phosphate into IO-NP to enhance its effects on demineralization. Then, we will evaluate the efficacy of
enhanced IO-NP/H2O2 for biofilm control in vitro using a mixed-species, cariogenic biofilm model (Aim 2). We
will further elucidate the biological actions of IO-NP/H2O2 using time-lapsed confocal and biophysical methods
to examine spatiotemporal degradation of EPS-matrix, bacterial killing and cohesiveness within intact biofilms.
The effects on enamel demineralization will be assessed using micro-hardness and micro-CT. In Aim 3, we will
evaluate the biocompatibility and efficacy of the developed IO-NP/H2O2 therapy in hindering cariogenic biofilms
and the onset of carious lesions in vivo using a rodent caries model with a clinically-relevant topical treatment
regimen. Successful...

## Key facts

- **NIH application ID:** 9827985
- **Project number:** 5R01DE025848-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Hyun Koo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $608,773
- **Award type:** 5
- **Project period:** 2016-12-09 → 2021-09-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9827985

## Citation

> US National Institutes of Health, RePORTER application 9827985, Biofilm Elimination and Caries Prevention using Multifunctional Nanocatalysts (5R01DE025848-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9827985. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*