细胞激素风暴
细胞因子
免疫系统
肺炎
免疫学
医学
促炎细胞因子
炎症
内科学
2019年冠状病毒病(COVID-19)
疾病
传染病(医学专业)
作者
Anwei Zhou,Kerong Chen,Ya Gao,Xinyuan Zhou,Zihan Tian,Weiwei Chen,Yurui Xu,Zhuo Chen,Xinghai Ning
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-08-19
卷期号:17 (17): 16461-16477
被引量:4
标识
DOI:10.1021/acsnano.3c00227
摘要
Cytokine storm is a common complication of COVID-19 pneumonia and has been proven to contribute to high mortality rates. However, current treatment approaches exhibit limited potential to balance immune response and overproduction of inflammatory cytokines, leading to poor therapeutic outcomes. Herein, a smart bioengineered neutrophil, Extinguisher, composed of live neutrophils encapsulating the liposome formulation of NF-κB suppressor MLN4924 and STING inhibitor H-151 (Lip@MH), is developed for alleviating the hyperinflammatory cytokine storm. Extinguisher inherits motility and chemotaxis characteristics of neutrophils, allowing for the specific delivery and sustained release of Lip@MH within inflamed tissues. Subsequently, Lip@MH effectively transports anti-inflammatory agents into macrophages and synergistically inhibits inflammatory pathways of NF-κB and STING, leading to decreased production of cytokines. In vivo studies demonstrate that Extinguisher not only selectively accumulates at the site of pneumonia caused by Pseudomonas aeruginosa-induced acute lung injury but inhibits the production of inflammatory factors through regulating NF-κB/STING signaling pathways, thereby effectively calming cytokine storm. Importantly, Extinguisher significantly improves therapeutic benefits and survival in mice with acute pneumonia. Therefore, Extinguisher represents an appropriate combination of cell therapy and immunoregulation for cytokine storm intervention and may bring insights into the treatment of COVID-19 pneumonia.
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