Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Orthodontics and Divisions of Pediatric Dentistry & Community Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Nat Commun. 2018 Jul 31;9(1):2920. doi: 10.1038/s41467-018-05342-x.
Ferumoxytol is a nanoparticle formulation approved by the U.S. Food and Drug Administration for systemic use to treat iron deficiency. Here, we show that, in addition, ferumoxytol disrupts intractable oral biofilms and prevents tooth decay (dental caries) via intrinsic peroxidase-like activity. Ferumoxytol binds within the biofilm ultrastructure and generates free radicals from hydrogen peroxide (HO), causing in situ bacterial death via cell membrane disruption and extracellular polymeric substances matrix degradation. In combination with low concentrations of HO, ferumoxytol inhibits biofilm accumulation on natural teeth in a human-derived ex vivo biofilm model, and prevents acid damage of the mineralized tissue. Topical oral treatment with ferumoxytol and HO suppresses the development of dental caries in vivo, preventing the onset of severe tooth decay (cavities) in a rodent model of the disease. Microbiome and histological analyses show no adverse effects on oral microbiota diversity, and gingival and mucosal tissues. Our results reveal a new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease.
Ferumoxytol 是一种纳米颗粒制剂，已获得美国食品和药物管理局批准，可用于全身治疗缺铁症。在这里，我们发现，Ferumoxytol 通过固有过氧化物酶样活性，除了可以破坏难治性口腔生物膜外，还可以预防龋齿（蛀牙）。Ferumoxytol 结合在生物膜超微结构内，并从过氧化氢（HO）中产生自由基，通过破坏细胞膜和降解细胞外聚合物基质来导致原位细菌死亡。在低浓度 HO 的组合下，Ferumoxytol 可抑制人源性离体生物膜模型中天然牙齿上生物膜的积累，并防止矿化组织的酸损伤。Ferumoxytol 和 HO 的局部口腔治疗可抑制体内龋齿的发展，在疾病的啮齿动物模型中可预防严重的蛀牙（龋洞）的发生。微生物组和组织学分析显示对口腔微生物多样性以及牙龈和粘膜组织没有不良影响。我们的结果揭示了 Ferumoxytol 作为一种局部治疗常见且昂贵的生物膜诱导性口腔疾病的新的生物医学应用。
