tetano
Editor, Senior Moderator
Nano Today
. 2021 Apr 8;101149.
doi: 10.1016/j.nantod.2021.101149. Online ahead of print.
Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm
Hyelim Kim[SUP] 1 2 [/SUP], Han Sol Lee[SUP] 1 [/SUP], June Hong Ahn[SUP] 3 [/SUP], Kyung Soo Hong[SUP] 3 [/SUP], Jong Geol Jang[SUP] 3 [/SUP], Jiseon An[SUP] 1 [/SUP], Yong-Hyeon Mun[SUP] 1 [/SUP], So-Yeol Yoo[SUP] 1 [/SUP], Yoon Jung Choi[SUP] 2 [/SUP], Mi-Young Yun[SUP] 4 [/SUP], Gyu Yong Song[SUP] 1 5 [/SUP], Jinmyoung Joo[SUP] 6 [/SUP], Dong Hee Na[SUP] 7 [/SUP], Hong Nam Kim[SUP] 2 8 [/SUP], Hee Ho Park[SUP] 9 [/SUP], Jae-Young Lee[SUP] 1 [/SUP], Wonhwa Lee[SUP] 10 [/SUP]
Affiliations
Abstract
In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. 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-?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 observed 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 accumulate the lung tissues and effectively downregulate NF-?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 patients, such as decreased cholesterol level and cytokine storm.
Keywords: 25-hydroxycholesterol; Didodecyldimethylammonium bromide; Lung-selective nanohybrids; Sepsis; Severe COVID-19.
. 2021 Apr 8;101149.
doi: 10.1016/j.nantod.2021.101149. Online ahead of print.
Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm
Hyelim Kim[SUP] 1 2 [/SUP], Han Sol Lee[SUP] 1 [/SUP], June Hong Ahn[SUP] 3 [/SUP], Kyung Soo Hong[SUP] 3 [/SUP], Jong Geol Jang[SUP] 3 [/SUP], Jiseon An[SUP] 1 [/SUP], Yong-Hyeon Mun[SUP] 1 [/SUP], So-Yeol Yoo[SUP] 1 [/SUP], Yoon Jung Choi[SUP] 2 [/SUP], Mi-Young Yun[SUP] 4 [/SUP], Gyu Yong Song[SUP] 1 5 [/SUP], Jinmyoung Joo[SUP] 6 [/SUP], Dong Hee Na[SUP] 7 [/SUP], Hong Nam Kim[SUP] 2 8 [/SUP], Hee Ho Park[SUP] 9 [/SUP], Jae-Young Lee[SUP] 1 [/SUP], Wonhwa Lee[SUP] 10 [/SUP]
Affiliations
- PMID: 33846686
- PMCID: PMC8026257
- DOI: 10.1016/j.nantod.2021.101149
Abstract
In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. 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-?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 observed 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 accumulate the lung tissues and effectively downregulate NF-?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 patients, such as decreased cholesterol level and cytokine storm.
Keywords: 25-hydroxycholesterol; Didodecyldimethylammonium bromide; Lung-selective nanohybrids; Sepsis; Severe COVID-19.