Bacterial biofilms are pervasive and recalcitrant to current antimicrobials, causing numerous infections. Iron oxide-nanozymes, including an FDA-approved formulation (ferumoxytol, FMX), show potential against biofilm infections via catalytic activation of hydrogen peroxide (H2O2). However, clinical evidence on its efficacy and therapeutic mechanisms is lacking. Here, we investigate whether FMX-nanozymes can treat chronic biofilm infections and compare their bioactivity to gold-standard sodium hypochlorite (NaOCl), a potent but caustic disinfectant. Clinical performance was assessed in patients with apical periodontitis, an intractable endodontic infection affecting half of the global adult population. Data show robust antibiofilm activity by a single application of FMX with H2O2 achieving results comparable to NaOCl without adverse effects. FMX binds efficiently to bacterial pathogens Enterococcus faecalis and Fusobacterium nucleatum and remains catalytically active without being affected by dental tissues. This allows for effective eradication of endodontic biofilms via on-site free-radical generation without inducing cytotoxicity. Unexpectedly, FMX promotes growth of stem cells of apical papilla (SCAP), with transcriptomic analyses revealing upregulation of proliferation-associated pathways and downregulation of cell-cycle suppressor genes. Notably, FMX activates SCAP pluripotency and WNT/NOTCH signaling that induces its osteogenic capacity. Together, we show FMX nanozymes are clinically effective against severe chronic biofilm infection with pathogen targeting and unique stem cell-stimulatory properties, offering a regenerative approach to antimicrobial therapy.

中文翻译：

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Ferumoxytol 纳米酶可有效靶向根尖周炎中的慢性生物膜感染。


细菌生物膜普遍存在，对当前的抗菌剂顽固不化，导致许多感染。氧化铁纳米酶，包括 FDA 批准的配方（氧化铁，FMX），通过催化活化过氧化氢 （H2O2） 显示出对抗生物膜感染的潜力。然而，缺乏关于其疗效和治疗机制的临床证据。在这里，我们研究了 FMX-纳米酶是否可以治疗慢性生物膜感染，并将其生物活性与金标准次氯酸钠 （NaOCl） 进行比较，这是一种有效但腐蚀性的消毒剂。在根尖周炎患者中评估了临床表现，根尖周炎是一种顽固性牙髓感染，影响了全球一半的成年人口。数据显示，单次施用 FMX 和 H 2 O 2 具有强大的抗生物膜活性，可获得与 NaOCl 相当的结果，且无不良影响。FMX 与细菌病原体粪肠球菌和有核梭杆菌有效结合，并保持催化活性，不受牙齿组织的影响。这允许通过现场自由基产生有效根除牙髓生物膜，而不会诱导细胞毒性。出乎意料的是，FMX 促进了顶端（SCAP） 干细胞的生长，转录组学分析揭示了增殖相关途径的上调和细胞周期抑制基因的下调。值得注意的是，FMX 激活 SCAP 多能性和 WNT/NOTCH 信号传导，从而诱导其成骨能力。总之，我们表明 FMX 纳米酶在临床上对严重的慢性生物膜感染有效，具有病原体靶向和独特的干细胞刺激特性，为抗菌治疗提供了一种再生方法。