期刊
ADVANCED SCIENCE
卷 7, 期 23, 页码 -出版社
WILEY
DOI: 10.1002/advs.202001940
关键词
Bioinspiration; COVID-19; DNase-I; Nanospheres; NETosis
资金
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2019R1C1C1006300, 2019R1A4A1028700, 2018R1C1B6001120, 2020R1A4A3078645, 2020R1A4A4079817]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2019M3C9A6091949]
- National Research Foundation of Korea (NRF) - Ministry of Science and ICT [2018M3A7B4071204]
- BK21 FOUR Project
- National Research Foundation of Korea [5199990514442, 4199990714142, 2019R1A4A1028700, 5199990614198, 2019M3C9A6091949, IBS-R015-D1-2020-A00, 2020R1A4A4079817, 2019R1C1C1006300] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The current outbreak of the beta-coronavirus (beta-Cov) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019. No specific antiviral treatments or vaccines are currently available. A recent study has reported that coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with neutrophil-specific plasma membrane rupture, and release excessive neutrophil extracellular traps (NETs) and extracellular DNAs (eDNAs). This mechanism involves the activation of NETosis, a neutrophil-specific programmed cell death, which is believed to play a crucial role in COVID-19 pathogenesis. Further progression of the disease can cause uncontrolled inflammation, leading to the initiation of cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. Herein, it is reported that DNase-I-coated melanin-like nanospheres (DNase-I pMNSs) mitigate sepsis-associated NETosis dysregulation, thereby preventing further progression of the disease. Recombinant DNase-I and poly(ethylene glycol) (PEG) are used as coatings to promote the lengthy circulation and dissolution of NET structure. The data indicate that the application of bioinspired DNase-I pMNSs reduce neutrophil counts and NETosis-related factors in the plasma of SARS-CoV-2 sepsis patients, alleviates systemic inflammation, and attenuates mortality in a septic mouse model. Altogether, the findings suggest that these nanoparticles have potential applications in the treatment of SARS-CoV-2-related illnesses and other beta-CoV-related diseases.
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