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J. Clin. Invest., Nov 26 2024, e183576 | https://doi.org/10.1172/JCI183576
Ferumoxytol nanozymes effectively target chronic biofilm infections in apical periodontitis
Alaa Babeer,1,2,3, Yuan Liu,2,4, Zhi Ren,2,5 Zhenting Xiang,2,5 Min Jun Oh,2,6 Nil Kanatha Pandey,2,7 Aurea Simon-Soro,2,8 Ranran Huang,9 Bekir Karabucak1, David P. Cormode,7 Chider Chen,5,9 Hyun Koo2,5
1Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2Biofilm Research Laboratories, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3Department of Oral Biology, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
4Department of Preventive and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
5Center for Innovation & Precision Dentistry, School of Dental Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
6Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
7Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
8Department of Stomatology, Faculty of Dentistry, University of Seville, Seville, Spain.
9Department of Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Address correspondence to: Hyun Koo
1Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2Biofilm Research Laboratories, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3Department of Oral Biology, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
4Department of Preventive and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
5Center for Innovation & Precision Dentistry, School of Dental Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
6Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
7Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
8Department of Stomatology, Faculty of Dentistry, University of Seville, Seville, Spain.
9Department of Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Address correspondence to: Hyun Koo
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 on its efficacy and therapeutic mechanisms is lacking. Here, we investigate whether FMX-nanozymes can treat chronic biofilm infections and compare their bioactivity to 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 NaOCl without adverse effects. FMX binds efficiently to 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 apical papilla (SCAP), 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, we show 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.
논문정보
- Research article
- 2024년 11월 (BRIC 등록일 2025-01-22)
- 국외 연구진
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