Bioinspired DNase-I-Coated Melanin-Like Nanospheres for Modulation of Infection-Associated NETosis Dysregulationopen access
- Authors
- Park, Hee Ho; Park, Wooram; Lee, Yun Young; Kim, Hyelim; Seo, Hee Seung; Choi, Dong Wook; Kwon, Ho-Keun; Na, Dong Hee; Kim, Tae-Hyung; Choy, Young Bin; Ahn, June Hong; Lee, Wonhwa; Park, Chun Gwon
- Issue Date
- Dec-2020
- Publisher
- WILEY
- Keywords
- Bioinspiration; COVID-19; DNase-I; Nanospheres; NETosis
- Citation
- ADVANCED SCIENCE, v.7, no.23
- Journal Title
- ADVANCED SCIENCE
- Volume
- 7
- Number
- 23
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/43433
- DOI
- 10.1002/advs.202001940
- ISSN
- 2198-3844
2198-3844
- Abstract
- 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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