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

被引：36

作者：

Park, Hee Ho ^{[1
]}

Kim, Hyelim ^{[2
,3
]}

Lee, Han Sol ^{[2
]}

Seo, Eun U. ^{[3
,4
]}

Kim, Ji-Eun ^{[2
,5
]}

Lee, Jee-Hyun ^{[5
]}

Mun, Yong-Hyeon ^{[2
]}

Yoo, So-Yeol ^{[2
]}

An, Jiseon ^{[2
]}

Yun, Mi-Young ^{[6
]}

Kang, Nae-Won ^{[7
,8
]}

Kim, Dae-Duk ^{[7
,8
]}

Na, Dong Hee ^{[9
]}

Hong, Kyung Soo ^{[10
,11
]}

Jang, Jong Geol ^{[10
,11
]}

Ahn, June Hong ^{[10
,11
]}

Bae, Jong-Sup ^{[12
]}

Song, Gyu Yong ^{[2
,5
]}

Lee, Jae-Young ^{[2
]}

Kim, Hong Nam ^{[3
,4
]}

Lee, Wonhwa ^{[13
]}

机构：

[1] Kangwon Natl Univ, Dept Biotechnol & Bioengn, Chunchon 24341, Gangwon Do, South Korea

[2] Chungnam Natl Univ, Coll Pharm, Daejeon 34134, South Korea

[3] Korea Inst Sci & Technol KIST, Brain Sci Inst, Seoul 02792, South Korea

[4] Korea Univ Sci & Technol, KIST Sch, Div Biomed Sci & Technol, Seoul 02792, South Korea

[5] AREZ Co Ltd, Daejeon 34134, South Korea

[6] Kwangju Womens Univ, Dept Beauty Sci, Gwangju 62396, South Korea

[7] Seoul Natl Univ, Coll Pharm, Seoul 08826, South Korea

[8] Seoul Natl Univ, Res Inst Pharmaceut Sci, Seoul 08826, South Korea

[9] Chung Ang Univ, Coll Pharm, Seoul 06974, South Korea

[10] Yeungnam Univ, Coll Med, Dept Internal Med, Div Pulmonol & Allergy, Daegu 42415, South Korea

[11] Yeungnam Univ, Med Ctr, Reg Ctr Resp Dis, Daegu 42415, South Korea

[12] Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Daegu 41566, South Korea

[13] Korea Res Inst Biosci & Biotechnol, Aging Res Ctr, Daejeon 34141, South Korea

来源：

BIOMATERIALS | 2021年 / 273卷

基金：

新加坡国家研究基金会;

关键词：

Albumin; Ginsenoside; COVID-19; NETosis; Cytokine storm; EXTRACELLULAR HISTONES; NANO-THERANOSTICS; COVID-19; SEPSIS; DEATH; SHOCK; TRAP;

D O I：

10.1016/j.biomaterials.2021.120827

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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.

引用

页数：14

共 85 条

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