Nano-decocted ferrous polysulfide coordinates ferroptosis-like death in bacteria for anti-infection therapy
Nano-decocted ferrous polysulfide coordinates ferroptosis-like death in bacteria for anti-infection therapy
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纳米煎煮的多硫化亚铁协调细菌铁死亡样死亡用于抗感染治疗
DOI：
10.1016/j.nantod.2020.100981
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发表时间：
2020-12-01
期刊：
影响因子：
17.4
通讯作者：
Gao, Lizeng
中科院分区：
文献类型：
--
作者：
Shen, Xinyu;Ma, Ruonan;Gao, Lizeng
抗菌纳米材料提供了有前途的替代策略，以应对由于耐药性恶化而导致的细菌感染的全球挑战。然而，由于潜在的细胞毒性和较差的生物相容性，很少有应用于细胞内细菌杀灭或体内治疗。在这里，我们提出了一个策略，以产生适合在体内抗感染治疗的配方，通过煎煮抗菌纳米材料。一种含有亚铁和多硫化物（Fe（II）S（n）aq）的水性配方，通过使用纳米硫化铁（nFeS）作为原料的煎煮过程制备。理论计算表明，硫原子被氧原子取代，导致多硫化物释放和铁溶解。从nFeS中提取的Fe（II）S（n）水溶液诱导细菌死亡，具有铁中毒样特征，包括铁富集、脂质过氧化和谷胱甘肽（GSH）耗尽。Fe（II）S（n）aq的抗菌作用依赖于亚铁离子，可被铁螯合剂、亚铁沉淀抑制剂和GSH抑制，而多硫化物则阻止亚铁离子的氧化并抵消GSH。此外，Fe（II）S（n）aq不仅在5 min内杀死高达99%的细菌，而且还抑制高达90%的细胞内金黄色葡萄球菌，而不引发对宿主细胞的细胞毒性。Fe（II）S（n）aq对感染性肺炎的治疗效果与万古霉素相当，并能显著延长脓毒症小鼠的生存期。这些结果表明，水性多硫化亚铁可诱导细菌中的铁凋亡样死亡，并可配制为抗感染治疗的抗菌替代品。(C)2020作者（S）爱思唯尔有限公司出版
Antibacterial nanomaterials provide promising alternative strategies to combat the global challenge of bacterial infection due to deteriorating resistance. However, few have been applied for intracellular bacteria killing or in vivo therapy due to potential cytotoxicity and poor biocompatibility. Here we present a strategy to generate formula suitable for in vivo anti-infective therapy by decocting antibacterial nanomaterial. An aqueous formula containing ferrous iron and polysulfide (Fe(II)S(n)aq) is prepared by a decoction procedure using nano-iron sulfide (nFeS) as raw substance. Theoretical calculation indicated that replacement of a sulfur atom by an oxygen atom occurred, resulting in polysulfide release and iron dissolution. The Fe(II)S(n)aq decocted from nFeS induced bacterial death with ferroptosis-like hallmarks, including iron enrichment, lipid peroxidation, and glutathione (GSH) depletion. The antibacterial action of Fe(II)S(n)aq was dependent on ferrous iron, which could be inhibited by iron chelators, ferroptosis inhibitors, and GSH, while the polysulfide prevented ferrous iron oxidation and counteracted GSH. Furthermore, Fe(II)S(n)aq not only killed up to 99 % of planktonic bacteria within 5 min, but also suppressed up to 90 % of intracellular Staphylococcus aureus without triggering cytotoxicity to host cell. Administration of Fe(II)S(n)aq achieved equivalent therapeutic effect to vancomycin for infectious pneumonia treatment and significantly prolonged the survival period of septic mice. These results indicate that aqueous ferrous polysulfide can induce ferroptosis- like death in bacteria and may be formulated as an antibacterial alternative for anti-infection therapy. (C) 2020 The Author( s). Published by Elsevier Ltd.