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Ferumoxytol 是一种纳米颗粒制剂，经美国食品药品监督管理局批准用于全身治疗缺铁症。本文我们还表明，ferumoxytol 还能破坏顽固的口腔生物膜，并通过内在过氧化物酶样活性预防龋齿。Ferumoxytol 结合生物膜超微结构，并从过氧化氢 (H 2 O 2 ) 产生自由基，通过细胞膜破坏和细胞外聚合物基质降解导致细菌原位死亡。与低浓度的 H 2 O 2结合，ferumoxytol 可在人源离体生物膜模型中抑制天然牙齿上生物膜的积聚，并防止矿化组织受到酸损伤。使用 ferumoxytol 和 H 2 O 2进行局部口服治疗可抑制体内龋齿的发展，防止啮齿动物模型中出现严重龋齿（蛀牙）。微生物组和组织学分析表明，该药物对口腔菌群多样性以及牙龈和黏膜组织均无不良影响。我们的研究结果揭示了Ferumoxytol作为一种常见且昂贵的生物膜诱发口腔疾病的局部治疗的全新生物医学应用。https://www.nature.com/articles/s41467-018-05342-x

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https://pubs.acs.org/doi/10.1021/acs.nanolett.1c02702
Ferumoxytol纳米粒子靶向导致人类口腔蛀牙的生物膜
重龋齿与缺铁性贫血有关，缺铁性贫血会给易感人群带来不成比例的负担。目前的治疗方法不足以应对致病性牙生物膜迅速积聚的严重病例，因此需要新的抗生物膜方法。本文展示了一种经美国食品药品监督管理局 (FDA) 批准用于治疗缺铁的纳米颗粒制剂——Ferumoxytol，它通过催化活化过氧化氢发挥替代治疗活性，靶向生物膜中的细菌病原体，并在口腔内人类疾病模型中抑制牙釉质的腐烂。数据显示，Ferumoxytol 氧化铁纳米颗粒 (FerIONP) 通过优先结合的方式，对含有变形链球菌的生物膜具有强大的抗菌特异性，这种结合方式通过原位自由基生成促进细菌杀灭。进一步分析表明，其靶向机制涉及 FerIONP 与病原体特异性葡聚糖结合蛋白的相互作用，而这些蛋白对共生链球菌的影响极小。此外，我们证明了FerIONP可以通过简单的比色反应检测天然牙齿上的致病生物膜。我们的研究结果提供了临床证据，并揭示了催化纳米粒子作为靶向抗感染纳米药物的诊疗潜力。

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https://www.nature.com/articles/s41467-018-05342-x
Ferumoxytol 是一种纳米颗粒制剂，经美国食品药品监督管理局批准用于全身治疗缺铁症。本文我们还表明，ferumoxytol 还能破坏顽固的口腔生物膜，并通过内在过氧化物酶样活性预防龋齿。Ferumoxytol 结合生物膜超微结构，并从过氧化氢 (H 2 O 2 ) 产生自由基，通过细胞膜破坏和细胞外聚合物基质降解导致细菌原位死亡。与低浓度的 H 2 O 2结合，ferumoxytol 可在人源离体生物膜模型中抑制天然牙齿上生物膜的积聚，并防止矿化组织受到酸损伤。使用 ferumoxytol 和 H 2 O 2进行局部口服治疗可抑制体内龋齿的发展，防止啮齿动物模型中出现严重龋齿（蛀牙）。微生物组和组织学分析表明，该药物对口腔菌群多样性以及牙龈和黏膜组织均无不良影响。我们的研究结果揭示了Ferumoxytol作为一种常见且昂贵的生物膜诱发口腔疾病的局部治疗的全新生物医学应用。

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https://penntoday.upenn.edu/news/nanozyme-therapy-prevents-harmful-dental-plaque-build

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The goal of this observational is study is to develop a protocol for root canal biofilms disinfection using a clinically approved and commercially available iron oxide nanoparticle formulation Ferumoxytol/H2O2 treatments. This protocol will be testing local single topical application of Ferumoxytol within the root canal system in patients going through routine root canal treatment, evaluate its potential as anti-biofilm treatment and compare it to the clinical gold standard disinfecting solution sodium hypochlorite (positive control) and saline (negative control).

Full description

Patients presenting to the Department of Endodontics, School of Dental Medicine, University of Pennsylvania for evaluation and routine endodontic treatment of infected, necrotic teeth with chronic apical periodontitis will be asked to take part in the study if they meet the inclusion criteria and volunteer to participate. After eligibility of the patient is confirmed, the patient will be assigned to treatments through the process of drawing lots from a box that was maintained in a locked cabinet. Before treatment, patients will be thoroughly informed about the nature, potential risks and alternatives of the study as well as the root canal treatment. Patients will be presented with a written consent form regarding the above mentioned study characteristics as well as the regular consent forms for the root canal therapy, including the consent form for endodontic treatement, acknowledgement of privacy practices and a patient understanding and informed consent form. Briefly, the patient will be anesthetized and the tooth isolated with rubber dam. 30% H2O2 followed by 3% NaOCl will be used to disinfect the tooth and the rubber dam. The removal of caries and the endodontic access will be carried out by sterile high-speed carbide burs.After access preparation with sterile burs and sterile saline irrigation, thermoplastic gutta percha was placed to temporarily block the orifice. The field, including the pulp chamber, is cleaned and disinfected as described previously. NaOCl is neutralized with 10% sodium thiosulfate. Contamination control sample (S0) will be taken from the internal cavosurface angle where the paper points will accidentally touch during sampling.After initial access to the root canal orifices, working length will be measured and a bacteriological sample will be taken from the targeted canals (S1). Sterile paper points will be placed into the canal, allowed to saturate and then transferred to a vial containing liquid dental transport media (LDT). For NaOCl group (Positive control), canals will be instrumented up to size 25/0.04 taper using 2mL of 3% NaOCl in between files. For Ferumoxytol/H2O2 group, canals will be instrumented up to size 25/0.04 taper using 2mL of a mixture of 6 mg/ml of Ferumoxytol with 3% H2O2. For saline only group, canals will be instrumented up to size 25/0.04 taper using 2mL of saline. When the final 25/0.04 taper apical size is reached, a second bacterial sample will be taken (S2). Before all samplings, sodium hypochlorite, Feramehe/ H2O2 and Saline. Canal contents will be deactivated with sodium thiosulphate for NaOCl,and saline wash will be used for Fer/H2O2 and saline treatments. A wash step with 1 mL saline was done to wash the deactivating solution, and paper points were used to dry the canals. A second bacterial sample was taken (S2) by placing LDT inside the canal, agitating it with 25/0.02 Hedstrom hand file, followed by absorbing the content with 2 paper points placed in the canal for 30 seconds each. The paper points will be placed inside a tube containing LDT. An additional step was included for all the test groups to evaluate if further irrigation after (S2) will lead to more reduction of bacterial counts inside the root canal system. This could inform future experiments evaluating the possibility of synergistic antimicrobial effects for the sequential Fer/H2O2 and NaOCl treatment. All canals in all groups were irrigated with 2 mL of 3% NaOCl (1 min), followed by ultrasonic irrigant activation for 30 seconds. This step was repeated once again making the total activation time 1 min and the total contact time of the irrigant 3 min. Upon completion of irrigation, a third bacterial sample (S3) was taken following the deactivation, washing, drying, and sampling steps as described previously. The remaining treatment sequences of the routine root canal therapy will be carried out after these procedures including further root-end enlargement and final routine irrigation protocol. The root canals will be dried with paper points, a medication (calcium hydroxide) will be placed and the teeth sealed with a temporary restoration. Patients will return after one to four weeks for completion of the root filling. For the any of the groups, the treatment procedures carried out during this investigation do not differ from the standard root canal treatment protocol with the exception of additional irrigation step with the experimental solution and the bacteriologic sampling procedures. The paper points used to take the bacteriological sampling will be transferred to the microbiology laboratory using a vial containing 1 ml of LDT. The laboratory procedures will be performed at the University of Pennsylvania Leon Levy Oral Health Sciences Building of the School of Dental Medicine in the Microbiology Laboratory Vial labels will contain information on tooth number, sample number (S0-S1-S2-S3) and the experimental group. The samples will be diluted and plated in culture plates. The culture plates will be incubated at 37°C in an anaerobic glove box containing 5% hydrogen, 5% CO2 and balance N2 for 5 days. After incubation the number of colony forming units will be determined by using a stereoscope. ANOVA and Students t-test will be used for statistical analysis.

https://ctv.veeva.com/study/a-new-clinical-use-of-ferumoxytol-nanoparticles-an-antibiofilm-treatment

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https://cdn.clinicaltrials.gov/large-docs/94/NCT06110494/Prot_SAP_003.pdf

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以下是关于将含有铁氧体（Fe₃O₄）纳米颗粒的费鲁莫昔托（Ferumoxytol）溶液与过氧化氢（H₂O₂）混合的制备方案，主要用于抗生物膜治疗的详细方法：
试剂与材料

费鲁莫昔托（Ferumoxytol）：FDA批准用于治疗缺铁性贫血的超小铁氧体纳米颗粒，具有类过氧化物酶活性。

过氧化氢（H₂O₂）：常用浓度为3%，用于激活纳米颗粒的催化活性。

配制步骤

溶液制备：

将3%浓度的过氧化氢溶液与费鲁莫昔托溶液按1:1体积比混合。

混合后，溶液呈现蓝色，表明自由基的生成。

反应机制：

费鲁莫昔托的Fe₃O₄核心具有类过氧化物酶活性，可催化H₂O₂分解生成羟基自由基（·OH）。

生成的自由基具有强氧化性，可破坏细菌细胞膜和生物膜基质，从而杀灭细菌。


应用示例

牙髓炎和根尖周炎的局部治疗：

在临床研究中，使用含费鲁莫昔托和过氧化氢的溶液对患有牙髓坏死和根尖周炎的患者进行局部治疗。

结果显示，该组合溶液在去除混合菌种生物膜方面表现出色，疗效与传统的次氯酸钠（NaOCl）相当，且无不良反应。

口腔生物膜的抑制：

在体外和动物模型中，费鲁莫昔托与过氧化氢的组合有效抑制了由变异链球菌等致龋菌引起的口腔生物膜的形成。

该组合不仅具有抗菌作用，还能促进牙髓干细胞的增殖和成骨分化。


注意事项

浓度控制：建议使用低浓度的费鲁莫昔托（如0.6%）和过氧化氢（如3%），以避免对口腔组织的刺激。

使用方法：该溶液主要用于局部应用，如牙科治疗，不建议系统性使用。

安全性：在临床应用中，需严格遵循剂量和使用方法，以确保安全性和有效性。


参考文献

Babeer, A., et al. (2025). "Ferumoxytol nanozymes effectively target chronic biofilm infections." JCI Insight.

Liu, Y., et al. (2021). "Ferumoxytol nanoparticles target biofilms causing tooth decay." Nano Letters.

Huang, Y., et al. (2022). "Repurposing ferumoxytol: Diagnostic and therapeutic applications." Theranostics.

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https://pmc.ncbi.nlm.nih.gov/articles/PMC11785919/#sd

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A novel treatment approach utilizing nanoparticles could be more effective at treating apical periodontitis during root canals.

Although use of the disinfectant sodium hypochlorite during root canals is the standard treatment option for apical periodontitis — the leading cause of tooth loss across the world — many patients may experience complications or treatment failure, according to a news article from Penn Today.

In a study published in The Journal of Clinical Investigation, researchers from the University of Pennsylvania analyzed whether the iron oxide nanoparticle formulation known as ferumoxytol could effectively manage apical periodontitis. They assigned a group of 44 patients to undergo a standard endodontic procedure followed by saline, sodium hypochlorite or ferumoxytol plus hydrogen peroxide.

The researchers demonstrated that ferumoxytol in combination with hydrogen peroxide had antibiofilm and stem cell-stimulating effects and was capable of inhibiting severe chronic biofilm infections. They highlighted that nearly 100% of bacterial counts were reduced without adverse effects. Further, the nanoparticles promoted the growth of stem cells as well as their osteogenic capacity.

The researchers concluded that the novel cost-effective nanotherapy approach could help patients maintain natural tooth structure and functionality.

宾夕法尼亚大学的研究人员合作，开发导致牙齿脱落的牙科感染的新治疗方案
宾夕法尼亚大学牙科医学院位于40街与Locust街交叉口。 刘陈尧 / 宾夕法尼亚日报
作者：索菲亚·尼曼
2025年2月27日
宾夕法尼亚大学牙科医学院、工程与应用科学学院以及佩雷尔曼医学院共同合作，开发了一种针对根尖牙周炎的新治疗方案，这是一种慢性牙齿感染，导致牙齿脱落，影响全球超过一半人口。

宾夕法尼亚大学创新与精准牙科中心最近在《临床研究杂志》上发表了一项研究，显示特异性纳米颗粒配方费鲁氧酚能减少根尖牙周炎。费鲁莫西托尔也是FDA批准的药物。根尖牙周炎是一种由生物膜——密集、粘稠的细菌群落——深附着在根管内引起的感染。根管治疗是目前的治疗方案，但由于并发症存在成功率的限制。

次氯酸钠是根管治疗中使用的消毒液，如果不在治疗区域内储存，可能会引发并发症，牙科学院牙髓学系主任兼教授贝基尔·卡拉布查克（Bekir Karabucak）表示。

“有效的根管消毒对治疗成功至关重要，”卡拉布查克说。“然而，在保护牙齿结构的同时针对微生物是一项挑战。现有程序需要机械方法和强力消毒剂来消除生物膜感染，但如果不小心使用，这些方法可能会损害周围组织。”

在实验阶段，创新与精准牙科中心使用铁氧糖醇/H2O2混合物治疗了44名患者，经过的手术实现了99.9%的细菌减少且无不良反应。

牙科学院口腔颌面外科助理教授陈奇德谈到了该项目最初的研究如何引领他们得出对未来牙齿健康的更大发现。

陈说：“最初只是对潜在毒性的简单调查，后来发展成了革命性的技术：一种能够消除顽固生物膜，同时再生组织以进行愈合的治疗，这是一种通过激活自身组织干细胞进行组织再生的新概念。”牙科学院教授贤九谈到了他对费鲁诺西托尔未来治疗可能性的兴奋。

“氧化铁纳米酶可能是一类具有变革性的新型治疗方法，既具抗生物膜又具组织再生特性，为抗菌治疗提供了再生途径，”库表示。“选择无限：它具有生物相容性，制造成本低廉，并且可以被掺入多种配方中。我们正在扩大纳米酶在口腔健康护理其他方面的应用。https://www.thedp.com/article/2025/02/penn-dental-engineering-root-canal-treatment