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Nano Today, Available online 8 April 2021 | https://doi.org/10.1016/j.nantod.2021.101149 Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm

Hyelim Kim^a,b,1, Han Sol Lee^a,1, June Hong Ahn^c,1, Kyung Soo Hong^c, Jong Geol Jang^c, Jiseon An^a, Yong-Hyeon Mun^a, So-Yeol Yoo^a, Yoon Jung Choi^a, Mi-Young Yun^d, Gyu Yong Song^a,e, Jinmyoung Joo^f, Dong Hee Na^g,*, Hong Nam Kim^b,h,*, Hee Ho Park^i,j,*, Jae-Young Lee^a,*, Wonhwa Lee^k,*

^aCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
^bBrain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
^cDivision of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu 42415, Republic of Korea
^dDepartment of Beauty Science, Kwangju Women’s University, Gwangju 62396, Republic of Korea
^eAREZ Co. Ltd., Daejeon 34134, Republic of Korea
^fDepartment of Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
^gCollege of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
^hDivision of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
ⁱDepartment of Biotechnology and Bioengineering, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea
^jInterdisciplinary Program in Biohealth-Machinery Convergence Engineering, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea
^kAging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea

¹These authors contributed equally: Hyelim Kim, Han Sol Lee, June Hong Ahn.

^*Corresponding authors.

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-κB- 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-κB 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.

논문정보

형식Research article
게재일2021년 04월 (BRIC 등록일 2021-04-21)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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