Nanozymes in Endodontics

Ferumoxytol Nanozymes for Biofilm Disruption: A Clinical Study

The antimicrobial efficacy and healing potential of clinically approved ferumoxytol nanozymes versus the standard 3% NaOCl irrigant will be evaluated in adults undergoing endodontic treatment. Building on prior protocols that demonstrated ferumoxytol nanozymes antimicrobial activity as a root canal irrigant, ferumoxytol solution will be applied topically, assessment of clinical and radiographical findings will determine its potential as a novel disinfection and its long-term outcome.

Study Overview

• Status: Not yet recruiting
• Conditions: Apical Periodontitis; Endodontic Disease; Root Canal Infection
• Intervention / Treatment: Drug: Nanozyme treatment; Drug: Control (Standard treatment)

Detailed Description

This study aims to fill critical knowledge gaps identified in prior clinical findings by optimizing the integration of nanozymes into endodontic workflows and thereby improving treatment outcomes for teeth with apical periodontitis. The study will evaluate the topical application of a low-dose ferumoxytol formulation (Feraheme/H2O2) within the prepared canal system of patients undergoing routine root canal therapy. Antimicrobial efficacy will be compared to the standard sodium hypochlorite irrigant via intracanal microbial sampling. Periapical tissue regeneration and long-term clinical outcomes will be assessed at 6-month and 1-year follow-up intervals using cone-beam computed tomography (CBCT).

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nadasinee Jaruchotiratanasakul, DDS, DScD Candidate; Phone Number: 2155264666; Email: nadaja@upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Dental Medicine, Department of Endodontics
      • Contact: Nadasinee Jaruchotiratanasakul, DDS, DScD; Phone Number: 215-526-4666; Email: nadaja@upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients willing to participate in the study.
2. Patients are 18 years or above.
3. Non-contributory medical history (Patient can be seen for regular dental appointment in PDM; ASA classes I and II).

4. Tooth requiring root canal treatment with radiographic presence of periapical radiolucency and

   1. responding to thermal sensitivity testing negatively (Difluordichlormethane at 50 °C, Endo-Ice,
   2. Coltène/Whaledent Inc., Cuyahoga Falls, Ohio) or a negative response to EPT testing.
5. Tooth with adequate remaining tooth structure for proper isolation with rubber dam.
6. No history of previous endodontic treatment on the tooth.
7. Teeth with single roots or multirooted teeth.

Exclusion Criteria:

1. Self-reported pregnancy.
2. Patients requiring antibiotic premedication prior to dental treatment.
3. Patients with multiple drug allergies.
4. Patients with known hypersensitivity to Ferumoxytol nanoparticles or any iron products.
5. Patients who are scheduled for MRI for the head region within three months after Ferumoxytol nanoparticles application.
6. Periodontal changes (pockets 3 mm, mobility Grade I, or gingival edema).
7. Patients who cannot return for a subsequent appointment or follow-ups.
8. Radiographic presence of resorptive processes.
9. Cracked and fractured teeth.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nanozyme treatment; After access preparation with sterile burs and sterile saline irrigation and working length determination, 2 mL of a mixture of Ferumoxytol (6mg/mL)/H2O2(3%) will be introduced into the canal. The root canal systems will be instrumented with XP-Shaper rotary files, a total of 8 mL of solution will be used, and a total contact time of 10 minutes.	Drug: Nanozyme treatment; Experimental arm: topical intra-canal irrigation with ferumoxytol (Feraheme®) diluted to 6 mg/mL in 0.1 M sodium acetate, activated with 3% H₂O₂. The solution is instilled into an isolated, dried canal, physically agitated for ~60 s to promote nanozyme activation and convective mixing, held for a brief contact time (<10 min), then aspirated per SOP; post-treatment intracanal sterile paper-point samples are collected. Topical nanozyme mechanism (catalytic ROS generation from low-dose H₂O₂), defined low topical dose and brief contact time (non-systemic).; Other Names: Feraheme; Ferumoxytol; Iron oxide nanoparticles
Active Comparator: Sodium hypochlorite; After access preparation with sterile burs and sterile saline irrigation and working length determination, 2 mL of a mixture of sodium hypochlorite (NaOCl) will be introduced into the canal. The root canal systems will be instrumented with XP-Shaper rotary files, a total of 8 mL of NaOCl solution will be used, and a total contact time of 10 minutes.	Drug: Control (Standard treatment); Control arm: standard clinical irrigation with 3% sodium hypochlorite (NaOCl) using matched total volume and institutional activation method, with identical pre/post sampling and follow-up.; Other Names: NaOCl; Sodium hypochlorite

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in bacterial count between the experimental group (Ferumoxytol/H2O2) and the standard of care (NaOCl) group.	By measuring reduction in bacteria colony forming units (CFU) before and after treatment for the experimental group (Ferumoxytol/H2O2) and the standard of care (NaOCl) group, then comparing the two groups. Samples 1-2 will be taken during the first root canal treatment visit. Sample 1 before cleaning or shaping the root canal. Sample 2 after cleaning and shaping of the root canal using laser or NaOCl. Sample 3 will be taken in the second visit, upon completion of final routine irrigation protocol.	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Periapical Bone Changes from Baseline in Periapical Radiographs at 6, 12, and 24 Months Follow Up	Periapical radiographs will be taken at baseline (preoperative) then at 6 months follow up post root canal filling. Radiographically, Following periapical index (PAI) by Órstavik 1986, description of radiographic findings: Normal periapical structures.; Small changes in the bone structure.; Change in the bone structure with mineral loss.; Periodontitis with a well-defined radiolucent area.; Severe periodontitis with exacerbating features. Success is defined as either complete (radiographic resolution of a periapical lesion - the radiographic sign of inflammatory processes surrounding a root tip) or incomplete healing (scar tissue formation) and failure includes uncertain healing (radiographic reduction of a periapical lesion or same lesion size) or unsatisfactory healing (increase in lesion size) as determined on the radiograph.	2 Years

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Publications and helpful links

General Publications

• 1. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats. Oral Surgery, Oral Medicine, Oral Pathology. 1965/09/01/ 1965;20(3):340-349. doi:https://doi.org/10.1016/0030-4220(65)90166-0 2. Bergenholtz G. Micro-organisms from necrotic pulp of traumatized teeth. Odontol Revy. 1974;25(4):347-58. 3. Kerekes K, Tronstad L. Long-term results of endodontic treatment performed with a standardized technique. Journal of Endodontics. 1979/03/01/ 1979;5(3):83-90. doi:https://doi.org/10.1016/S0099-2399(79)80154-5 4. Bukhari S, Kim D, Liu Y, Karabucak B, Koo H. Novel Endodontic Disinfection Approach Using Catalytic Nanoparticles. J Endod. May 2018;44(5):806-812. doi:10.1016/j.joen.2017.12.003 5. Ricucci D, Siqueira JF, Jr. Biofilms and apical periodontitis: study of prevalence and association with clinical and histopathologic findings. J Endod. Aug 2010;36(8):1277-88. doi:10.1016/j.joen.2010.04.007 6. SJÖGREN U, FIGDOR D, PERSSON S, SUNDQVIST G. Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis. International Endodontic Journal. 1997;30(5):297-306. doi:https://doi.org/10.1046/j.1365-2591.1997.00092.x 7. Ricucci D, Siqueira JF, Bate AL, Pitt Ford TR. Histologic Investigation of Root Canal-treated Teeth with Apical Periodontitis: A Retrospective Study from Twenty-four Patients. Journal of Endodontics. 2009/04/01/ 2009;35(4):493-502. doi:https://doi.org/10.1016/j.joen.2008.12.014 8. Babeer A, Liu Y, Ren Z, et al. Ferumoxytol nanozymes effectively target chronic biofilm infections in apical periodontitis. J Clin Invest. Nov 26 2024;doi:10.1172/jci183576 9. Huang Y, Liu Y, Pandey NK, et al. Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention. Nature Communications. 2023/09/29 2023;14(1):6087. doi:10.1038/s41467-023-41687-8

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Nanotechnology; iron oxide nanoparticles; Root canal irrigants; Nanozymes
• Additional Relevant MeSH Terms: Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Periapical Diseases; Jaw Diseases; Tooth Diseases; Periodontitis; Periapical Periodontitis; Dental Pulp Diseases; Inorganic Chemicals; Chlorine Compounds; Manufactured Materials; Technology, Industry, and Agriculture; Oxides; Oxygen Compounds; Ferric Compounds; Iron Compounds; Ferrous Compounds; Minerals; Hypochlorous Acid; Sodium Compounds; Nanostructures; Metal Nanoparticles; Nanoparticles; Ferrosoferric Oxide; Sodium Hypochlorite; Magnetic Iron Oxide Nanoparticles
• Other Study ID Numbers: 859377

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only the participants chart numbers were collected during the study. The study protocol, statistical analysis plan, and informed consent form will be published as supporting information with the final manuscript
• IPD Sharing Time Frame: The supporting information will be available with the publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes