Hyelim, Kim Lee, H.S. Ahn, J.H. Hong, K.S. Jang, J.G. An, J. Mun, Y.-H. Yoo, S.-Y. Choi, Y.J. Yun, M.-Y. Song, G.Y. Joo, J. Na, D.H. Kim, Hong Nam Park, H.H. Lee, J.-Y. Lee, W. 2024-01-19T14:33:14Z 2024-01-19T14:33:14Z 2021-09-02 2021-06 1748-0132 https://pubs.kist.re.kr/handle/201004/116963 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. ？ 2021 The Author(s) English Elsevier B.V. Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm Article 10.1016/j.nantod.2021.101149 1 Nano Today, v.38 Nano Today 38 Y scie scopus 000670246400002 2-s2.0-85104142126 Chemistry, Multidisciplinary Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article Clinical conditions Didodecyldimethylammonium bromide Intracellular cholesterol Severe acute respiratory syndrome coronavirus Signaling pathways Therapeutic intervention Diseases 25 hydroxycholesterol alanine aminotransferase aspartate aminotransferase beta actin C reactive protein cholesterol clostridiopeptidase A creatinine real time polymerase chain reaction cryopyrin cytokine didodecyldimethylammonium bromide double stranded DNA high density lipoprotein cholesterol immunoglobulin enhancer binding protein inflammasome intercellular adhesion molecule 1 interleukin 10 interleukin 1beta interleukin 6 lactate dehydrogenase liposome low density lipoprotein cholesterol monocyte chemotactic protein 1 nitrogen nox protein reactive oxygen metabolite reduced nicotinamide adenine dinucleotide phosphate oxidase 2 sn 50 srebf2 protein sterol regulatory element binding protein 2 tumor necrosis factor unclassified drug urea animal cell animal experiment animal model animal tissue Article cecal ligation and puncture-induced sepsis cholesterol level controlled study coronavirus disease 2019 cytokine storm data analysis software disease association down regulation drug accumulation drug efficacy enzyme linked immunosorbent assay female hemagglutination high performance liquid chromatography human human cell lung parenchyma male mortality rate mouse nonhuman peripheral blood mononuclear cell Biological organs Cholesterol Patient treatment Storms Acute respiratory distress syndrome Cholesterol levels Severe acute respiratory syndrome coronavirus 2 signal transduction symptom theranostic nanomedicine transmission electron microscopy virus replication 25-hydroxycholesterol Didodecyldimethylammonium bromide Lung-selective nanohybrids Sepsis Severe COVID-19