Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm

• DOI: 10.1016/j.nantod.2021.101149
• Publication Date: 2021-04-08T01:58:10Z
• Authors: Hyelim Kim; Han Sol Lee; June Hong Ahn; Kyung Soo Hong; Jong Geol Jang; Jiseon An; Yong-Hyeon Mun; So-Yeol Yoo; Yoon Jung Choi; Mi-Young Yun; Gyu Yong Song; Jinmyoung Joo; Dong Hee Na; Hong Nam Kim; Hee Ho Park; Jae-Young Lee; Wonhwa Lee
• Keywords: Cytokine Storm; Pathogenesis

In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2), global efforts are focused on development of new therapeutic interventions. For treatment COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades lung via ACE2 receptors and causes pneumonia. Similarly, recent reports have shown association COVID-19 with decreased 25-hydroxycholesterol (25-HC) increased cytokine levels. This mechanism, which involves activation inflammatory NF-κB- SREBP2-mediated inflammasome signaling pathways, is believed play a crucial role in pathogenesis, inducing distress (ARDS) sepsis. To resolve those clinical conditions observed patients, we report 25-HC didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) drug candidate for restoration intracellular cholesterol level suppression storm. Our data demonstrate that 25-HC@DDAB can selectively accumulate tissues effectively downregulate NF-κB SREBP2 pathways patient-derived PBMCs, reducing Altogether, our findings suggest promising symptoms associated such