Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine stormopen access
- Authors
- Kim, Hyelim; Lee, Han Sol; Ahn, June Hong; Hong, Kyung Soo; Jang, Jong Geol; An, Jiseon; Mun, Yong-Hyeon; Yoo, So-Yeol; Choi, Yoon Jung; Yun, Mi-Young; Song, Gyu Yong; Joo, Jinmyoung; Na, Dong Hee; Kim, Hong Nam; Park, Hee Ho; Lee, Jae-Young; Lee, Wonhwa
- Issue Date
- Jun-2021
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Severe COVID-19; Lung-selective nanohybrids; Sepsis; 25-hydroxycholesterol; Didodecyldimethylammonium bromide
- Citation
- NANO TODAY, v.38
- Indexed
- SCIE
SCOPUS
- Journal Title
- NANO TODAY
- Volume
- 38
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/190289
- DOI
- 10.1016/j.nantod.2021.101149
- ISSN
- 1748-0132
- Abstract
- In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syn-drome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic in-terventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades the lung via ACE2 receptors and causes severe pneumonia. Similarly, recent reports have shown the association of COVID-19 with decreased 25-hydroxycholesterol (25-HC) and increased cytokine levels. This mechanism, which involves the activation of inflammatory NF-kappa B-and SREBP2-mediated inflammasome signaling pathways, is believed to play a crucial role in COVID-19 pathogenesis, inducing acute respiratory distress syndrome (ARDS) and sepsis. To resolve those clinical conditions ob-served in severe SARS-CoV-2 patients, we report 25-HC and didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) as a COVID-19 drug candidate for the restoration of intracellular cholesterol level and suppression of cytokine storm. Our data demonstrate that 25-HC@DDAB can selectively accu-mulate the lung tissues and effectively downregulate NF-kappa B and SREBP2 signaling pathways in COVID-19 patient-derived PBMCs, reducing inflammatory cytokine levels. Altogether, our findings suggest that 25-HC@DDAB is a promising candidate for the treatment of symptoms associated with severe COVID-19 pa-tients, such as decreased cholesterol level and cytokine storm.
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