Oxidation of Hydrogen Sulfide to Polysulfide and Thiosulfate by a Carbon Nanozyme: Therapeutic Implications with an Emphasis on Down Syndrome
Oxidation of Hydrogen Sulfide to Polysulfide and Thiosulfate by a Carbon Nanozyme: Therapeutic Implications with an Emphasis on Down Syndrome
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DOI：
10.1002/adma.202211241
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发表时间：
2023-07-23
影响因子：
29.4
通讯作者：
Kent，Thomas A.
中科院分区：
文献类型：
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作者：
Derry，Paul J.;Liopo，Anton V.;Kent，Thomas A.
硫化氢(H_2S)是人体硫代谢过程中产生的一种有毒、潜在有毒但又必不可少的气体。在唐氏综合征(DS)中，H2S的产生增加，并与线粒体功能下降有关。因此，将硫化氢作为一种稳定的氧化物从体内排出，可能是减少硫化氢在DS中有害影响的一种方法。在这份报告中，我们描述了聚乙二醇亲水碳团簇(聚乙二醇亲水碳簇)和聚乙二醇氧化型活性碳(聚乙二醇氧化型活性碳)催化硫化氢氧化成多硫化物(HS2+n−)和硫代硫酸盐(S2O32−)，氧化碳纳米酶(OCNs)的例子。我们发现OCNs以剂量依赖的方式将H_2S氧化成多硫化物和S_2O_32−。该反应依赖于O2和OCNs上的苯醌基团的存在。在DS供者淋巴细胞中，我们发现与未经处理的DS淋巴细胞相比，OCNs增加了多硫化物的产生、增殖，并对额外的硫化氢毒性水平提供了保护。最后，在Dp16和Ts65Dn小鼠DS模型中，我们发现OCNs恢复了破骨细胞的分化。这一新的行动表明，对于以DS为例的过量硫化氢的情况，可能会很容易地转化为临床。
Hydrogen sulfide (H2S) is a noxious, potentially poisonous, but necessary gas produced from sulfur metabolism in humans. In Down Syndrome (DS), the production of H2S is elevated and associated with degraded mitochondrial function. Therefore, removing H2S from the body as a stable oxide could be an approach to reducing the deleterious effects of H2S in DS. In this report we describe the catalytic oxidation of hydrogen sulfide (H2S) to polysulfides (HS2+n−) and thiosulfate (S2O32−) by poly(ethylene glycol) hydrophilic carbon clusters (PEG‐HCCs) and poly(ethylene glycol) oxidized activated charcoal (PEG‐OACs), examples of oxidized carbon nanozymes (OCNs). We show that OCNs oxidize H2S to polysulfides and S2O32−in a dose‐dependent manner. The reaction is dependent on O2and the presence of quinone groups on the OCNs. In DS donor lymphocytes we found that OCNs increased polysulfide production, proliferation, and afforded protection against additional toxic levels of H2S compared to untreated DS lymphocytes. Finally, in Dp16 and Ts65DN murine models of DS, we found that OCNs restored osteoclast differentiation. This new action suggests potential facile translation into the clinic for conditions involving excess H2S exemplified by DS.