Ferumoxytol Nanoparticles Target Biofilms Causing Tooth Decay in the Human Mouth.

Ferumoxytol Nanoparticles Target Biofilms Causing Tooth Decay in the Human Mouth.
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DOI:
10.1021/acs.nanolett.1c02702
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发表时间:
2021-11-24
期刊:
影响因子:
10.8
通讯作者:
Koo H
Koo H
中科院分区:
材料科学1区
文献类型:
--
作者:
Liu Y;Huang Y;Kim D;Ren Z;Oh MJ;Cormode DP;Hara AT;Zero DT;Koo H

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严重的蛀牙与缺铁性贫血有关,缺铁性贫血给易感人群带来了不成比例的负担。在致病性牙齿生物膜迅速积累的严重病例中,目前的治疗方法还不够,需要新的抗生物膜方法。在这里,我们展示了 ferumoxytol(一种经美国食品和药物管理局批准用于治疗缺铁的纳米颗粒制剂)通过过氧化氢的催化激活发挥替代治疗活性,该活性针对生物膜中的细菌病原体,并在人类口腔疾病模型中抑制牙釉质腐烂。数据显示,ferumoxytol 氧化铁纳米颗粒 (FerIONP) 通过优先结合对含有变形链球菌的生物膜具有强大的抗菌特异性,通过原位自由基生成促进细菌杀灭。进一步的分析表明,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,这对共生链球菌的影响很小。此外,我们证明 FerIONP 可以通过简单的比色反应检测天然牙齿上的致病性生物膜。我们的研究结果提供了临床证据和催化纳米颗粒作为靶向抗感染纳米药物的治疗诊断潜力。
Severe tooth decay has been associated with iron deficiency anemia that disproportionally burdens susceptible populations. Current modalities are insufficient in severe cases where pathogenic dental biofilms rapidly accumulate, requiring new antibiofilm approaches. Here, we show that ferumoxytol, a Food and Drug Administration-approved nanoparticle formulation for treating iron deficiency, exerts an alternative therapeutic activity via the catalytic activation of hydrogen peroxide, which targets bacterial pathogens in biofilms and suppresses tooth enamel decay in an intraoral human disease model. Data reveal the potent antimicrobial specificity of ferumoxytol iron oxide nanoparticles (FerIONP) against biofilms harboring Streptococcus mutans via preferential binding that promotes bacterial killing through in situ free-radical generation. Further analysis indicates that the targeting mechanism involves interactions of FerIONP with pathogen-specific glucan-binding proteins, which have a minimal effect on commensal streptococci. In addition, we demonstrate that FerIONP can detect pathogenic biofilms on natural teeth via a facile colorimetric reaction. Our findings provide clinical evidence and the theranostic potential of catalytic nanoparticles as a targeted anti-infective nanomedicine.
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