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.

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).

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.

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

The supporting information will be available with the publication.