Ferumoxytol nanozymes effectively target chronic biofilm infections in apical periodontitis
Alaa Babeer, … , Chider Chen, Hyun Koo
Alaa Babeer, … , Chider Chen, Hyun Koo
Published November 26, 2024
Citation Information: J Clin Invest. 2025;135(3):e183576. https://doi.org/10.1172/JCI183576.
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Ferumoxytol nanozymes effectively target chronic biofilm infections in apical periodontitis

Abstract

Bacterial biofilms are pervasive and recalcitrant to current antimicrobials, causing numerous infections. Iron oxide nanozymes, including an FDA-approved formulation, ferumoxytol (FMX), show potential against biofilm infections via catalytic activation of hydrogen peroxide (H2O2). However, clinical evidence regarding the efficacy and therapeutic mechanisms of FMX is lacking. Here, we investigate whether FMX nanozymes can treat chronic biofilm infections and compare their bioactivity to that of the gold standard sodium hypochlorite (NaOCl), a potent but caustic disinfectant. Clinical performance was assessed in patients with apical periodontitis, an intractable endodontic infection affecting half of the global adult population. Data show robust antibiofilm activity by a single application of FMX with H2O2 achieving results comparable to those seen with NaOCl without adverse effects. FMX binds efficiently to the bacterial pathogens Enterococcus faecalis and Fusobacterium nucleatum and remains catalytically active without being affected by dental tissues. This allows for effective eradication of endodontic biofilms via on-site free radical generation without inducing cytotoxicity. Unexpectedly, FMX promotes growth of stem cells of the apical papilla (SCAPs), with transcriptomic analyses revealing upregulation of proliferation-associated pathways and downregulation of cell cycle suppressor genes. Notably, FMX activates SCAP pluripotency and WNT/NOTCH signaling that induces its osteogenic capacity. Together, these results show that FMX nanozymes are clinically effective against severe chronic biofilm infection with pathogen targeting and unique stem cell–stimulatory properties, offering a regenerative approach to antimicrobial therapy.

Authors

Alaa Babeer, Yuan Liu, Zhi Ren, Zhenting Xiang, Min Jun Oh, Nil Kanatha Pandey, Aurea Simon-Soro, Ranran Huang, Bekir Karabucak, David P. Cormode, Chider Chen, Hyun Koo

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Figure 5

Surface retention, in situ catalysis, and regenerative potential of FMX nanozymes.

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Surface retention, in situ catalysis, and regenerative potential of FMX ...
(A) Amount of FMX retained in treated biofilms after 10 minutes of treatment measured by ICP-OES (n = 6). (B) Left: A representative environmental scanning electron microscope image of the FMX-treated biofilm and the corresponding elemental mapping image showing iron ion (yellow) distribution. Scale bars: 10 μm. Right: EDS spectra of untreated and FMX-treated biofilms. (C) Catalytic activity of retained FMX in biofilms (n = 12). (D) Amount of FMX bound to bacterial cells after 10 minutes of treatment (n = 6). (E) Ki67 staining showed that 0.1 mg/mL or higher concentrations of FMX significantly increased SCAP proliferation after a 24-hour treatment. Scale bar: 25 μm. Original magnification × 20. (F) Quantitative analysis of the percentage of Ki67+ cells after treatment (n = 3). (G) Heatmap of transcriptomics analysis showing genes differentially regulated after 1 mg/mL FMX treatment for 24 hours. Gene expression is shown in normalized log2 counts per million. Differentially expressed genes were selected based on a 4-fold change. (H) qPCR assay confirmed that cell cycle genes were highly activated while cell cycle suppressor genes were greatly diminished after FMX treatment. Statistical analyses were performed using Welch’s 2-tailed t test (A and C), ANOVA followed by Tukey’s test (D), or ANOVA followed by Dunnett’s test (F and H) for multiple comparisons. All values are reported as mean ± SD, *P < 0.05, ***P < 0.001, ****P < 0.0001; ns, not significant.