Department of Radiology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, PR China.
Intelligent Nanomedicine Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, PR China.
Biomaterials. 2021 Dec;279:121237. doi: 10.1016/j.biomaterials.2021.121237. Epub 2021 Nov 2.
As a vital bacteria-secreted toxin, hydrogen peroxide (HO) can destroy infected tissues and increase vascular permeability, leading to life-threatening systemic bacteremia or sepsis. No strategy that can alleviate HO-induced injury and prevent systemic sepsis has been reported. Herein, as a proof of concept, we demonstrate the use of HO-reactive metal-organic framework nanosystems (MOFs) for treating HO-secreting bacteria. In mice infected with Streptococcus pneumoniae (S. pneumoniae) isolated from patients, MOFs efficiently accumulate in the lungs after systemic administration due to infection-induced alveolar-capillary barrier dysfunction. Moreover, MOFs sequester pneumococcal HO, reduce endothelial DNA damage, and prevent systemic dissemination of bacteria. In addition, this nanosystem exhibits excellent chemodynamic bactericidal effects against drug-resistant bacteria. Through synergistic therapy with the antibiotic ampicillin, MOFs eliminate over 98% of invading S. pneumoniae, resulting in a survival rate of greater than 90% in mice infected with a lethal dose of S. pneumoniae. This work opens up new paths for the clinical treatment of toxin-secreting bacteria.
过氧化氢（HO）作为一种重要的细菌分泌毒素，可以破坏感染组织并增加血管通透性，导致危及生命的全身菌血症或败血症。目前还没有报道任何可以减轻 HO 诱导损伤并预防全身败血症的策略。在这里，作为一个概念验证，我们展示了使用 HO 反应性金属有机骨架纳米系统（MOFs）来治疗分泌 HO 的细菌。在感染了从患者中分离出的肺炎链球菌（S. pneumoniae）的小鼠中，由于感染引起的肺泡毛细血管屏障功能障碍，MOFs 在全身给药后能够有效地在肺部积聚。此外，MOFs 隔离肺炎链球菌 HO，减少内皮 DNA 损伤，并防止细菌的全身传播。此外，该纳米系统对耐药菌具有优异的化学动力学杀菌作用。通过与抗生素氨苄西林协同治疗，MOFs 消除了超过 98%的入侵肺炎链球菌，使感染致死剂量肺炎链球菌的小鼠的存活率大于 90%。这项工作为临床治疗分泌毒素的细菌开辟了新的途径。
