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人源化细胞伪装纳米磁体清除剂可恢复菌血症啮齿动物模型的免疫稳态

Human Cell-Camouflaged Nanomagnetic Scavengers Restore Immune Homeostasis in a Rodent Model with Bacteremia.

机构信息

Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), UNIST gil 50, Ulsan, 44919, Republic of Korea.

出版信息

Small. 2022 Oct;18(40):e2203746. doi: 10.1002/smll.202203746. Epub 2022 Sep 7.

Abstract

Bloodstream infection caused by antimicrobial resistance pathogens is a global concern because it is difficult to treat with conventional therapy. Here, scavenger magnetic nanoparticles enveloped by nanovesicles derived from blood cells (MNVs) are reported, which magnetically eradicate an extreme range of pathogens in an extracorporeal circuit. It is quantitatively revealed that glycophorin A and complement receptor (CR) 1 on red blood cell (RBC)-MNVs predominantly capture human fecal bacteria, carbapenem-resistant (CR) Escherichia  coli, and extended-spectrum beta-lactamases-positive (ESBL-positive) E. coli, vancomycin-intermediate Staphylococcus aureus (VISA), endotoxins, and proinflammatory cytokines in human blood. Additionally, CR3 and CR1 on white blood cell-MNVs mainly contribute to depleting the virus envelope proteins of Zika, SARS-CoV-2, and their variants in human blood. Supplementing opsonins into the blood significantly augments the pathogen removal efficiency due to its combinatorial interactions between pathogens and CR1 and CR3 on MNVs. The extracorporeal blood cleansing enables full recovery of lethally infected rodent animals within 7 days by treating them twice in series. It is also validated that parameters reflecting immune homeostasis, such as blood cell counts, cytokine levels, and transcriptomics changes, are restored in blood of the fatally infected rats after treatment.

摘要

抗微生物药物耐药性病原体引起的血流感染是一个全球性的问题,因为用传统疗法很难治疗。在这里,我们报告了一种由血细胞衍生的纳米囊泡包裹的 scavenger 磁性纳米颗粒(MNVs),它可以在体外循环中通过磁场消除极广泛的病原体。定量研究表明,红细胞(RBC)-MNVs 上的糖蛋白 A 和补体受体(CR)1 主要捕获人类粪便细菌、耐碳青霉烯类(CR)大肠杆菌和产超广谱β-内酰胺酶阳性(ESBL-阳性)大肠杆菌、万古霉素中介金黄色葡萄球菌(VISA)、内毒素和人血中的促炎细胞因子。此外,白细胞-MNVs 上的 CR3 和 CR1 主要有助于耗尽人血中寨卡病毒、SARS-CoV-2 及其变体的病毒包膜蛋白。由于病原体与 MNVs 上的 CR1 和 CR3 之间的组合相互作用,向血液中补充调理素可显著提高病原体清除效率。通过两次连续治疗,体外血液净化可使感染致死的啮齿动物在 7 天内完全恢复。实验还验证了治疗后,致死性感染大鼠血液中的免疫稳态参数(如血细胞计数、细胞因子水平和转录组学变化)得到恢复。

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