PEGylated nanoparticle albumin-bound steroidal ginsenoside derivatives ameliorate SARS-CoV-2-mediated hyper-inflammatory responses

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin l...

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Published in	Biomaterials Vol. 273; p. 120827
Main Authors	Park, Hee Ho, Kim, Hyelim, Lee, Han Sol, Seo, Eun U, Kim, Ji-Eun, Lee, Jee-Hyun, Mun, Yong-Hyeon, Yoo, So-Yeol, An, Jiseon, Yun, Mi-Young, Kang, Nae-Won, Kim, Dae-Duk, Na, Dong Hee, Hong, Kyung Soo, Jang, Jong Geol, Ahn, June Hong, Bae, Jong-Sup, Song, Gyu Yong, Lee, Jae-Young, Kim, Hong Nam, Lee, Wonhwa
Format	Journal Article
Language	English
Published	Netherlands Elsevier Ltd 01.06.2021 The Authors. Published by Elsevier Ltd
Subjects	Albumin Albumins animal models Animals bioactive properties biocompatible materials blood coagulation blood vessels coagulation COVID-19 COVID-19 infection Cytokine storm cytokines Ginsenoside ginsenosides Ginsenosides - pharmacology histones Humans inflammation Nanoparticles NETosis Polyethylene Glycols SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 survival rate therapeutics COVID-19 Albumin NETosis Cytokine storm Ginsenoside
Online Access	Get full text
ISSN	0142-9612 1878-5905 1878-5905
DOI	10.1016/j.biomaterials.2021.120827

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Abstract	The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm.
AbstractList	The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm. The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm.The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm.
ArticleNumber	120827
Author	Seo, Eun U Jang, Jong Geol Lee, Wonhwa Kang, Nae-Won Lee, Jae-Young Lee, Jee-Hyun Kim, Dae-Duk Kim, Hyelim Song, Gyu Yong Yun, Mi-Young Park, Hee Ho Kim, Ji-Eun Yoo, So-Yeol Mun, Yong-Hyeon Hong, Kyung Soo Kim, Hong Nam Ahn, June Hong Bae, Jong-Sup Na, Dong Hee Lee, Han Sol An, Jiseon
Author_xml	– sequence: 1 givenname: Hee Ho surname: Park fullname: Park, Hee Ho organization: Department of Biotechnology and Bioengineering, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea – sequence: 2 givenname: Hyelim surname: Kim fullname: Kim, Hyelim organization: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea – sequence: 3 givenname: Han Sol surname: Lee fullname: Lee, Han Sol organization: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea – sequence: 4 givenname: Eun U surname: Seo fullname: Seo, Eun U organization: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea – sequence: 5 givenname: Ji-Eun surname: Kim fullname: Kim, Ji-Eun organization: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea – sequence: 6 givenname: Jee-Hyun surname: Lee fullname: Lee, Jee-Hyun organization: AREZ Co. Ltd., Daejeon, 34134, Republic of Korea – sequence: 7 givenname: Yong-Hyeon surname: Mun fullname: Mun, Yong-Hyeon organization: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea – sequence: 8 givenname: So-Yeol surname: Yoo fullname: Yoo, So-Yeol organization: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea – sequence: 9 givenname: Jiseon surname: An fullname: An, Jiseon organization: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea – sequence: 10 givenname: Mi-Young surname: Yun fullname: Yun, Mi-Young organization: Department of Beauty Science, Kwangju Women's University, Gwangju, 62396, Republic of Korea – sequence: 11 givenname: Nae-Won surname: Kang fullname: Kang, Nae-Won organization: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea – sequence: 12 givenname: Dae-Duk surname: Kim fullname: Kim, Dae-Duk organization: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea – sequence: 13 givenname: Dong Hee surname: Na fullname: Na, Dong Hee organization: College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea – sequence: 14 givenname: Kyung Soo surname: Hong fullname: Hong, Kyung Soo organization: Division 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 – sequence: 15 givenname: Jong Geol surname: Jang fullname: Jang, Jong Geol organization: Division 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 – sequence: 16 givenname: June Hong surname: Ahn fullname: Ahn, June Hong organization: Division 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 – sequence: 17 givenname: Jong-Sup surname: Bae fullname: Bae, Jong-Sup email: baejs@knu.ac.kr organization: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea – sequence: 18 givenname: Gyu Yong surname: Song fullname: Song, Gyu Yong email: gysong@cnu.ac.kr organization: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea – sequence: 19 givenname: Jae-Young surname: Lee fullname: Lee, Jae-Young email: jaeyoung@cnu.ac.kr organization: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea – sequence: 20 givenname: Hong Nam surname: Kim fullname: Kim, Hong Nam email: hongnam.kim@kist.re.kr organization: Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea – sequence: 21 givenname: Wonhwa orcidid: 0000-0003-4336-5221 surname: Lee fullname: Lee, Wonhwa email: wonhwalee@kribb.re.kr organization: Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea
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Keywords	COVID-19 Albumin NETosis Cytokine storm Ginsenoside
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this study: Hee Ho Park, Hyelim Kim, Han Sol Lee, Eun U Seo, Ji-Eun Kim.
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Snippet	The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a...
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Title	PEGylated nanoparticle albumin-bound steroidal ginsenoside derivatives ameliorate SARS-CoV-2-mediated hyper-inflammatory responses
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