Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates
Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines. The nanoDEX, made by encapsulating DEX with the iSEND, efficiently promoted the anti-inflammation effect of DEX in an acute pneumonia mouse model and suppressed DEX-induced bone density reduction in an osteoporosis rat model. Relative to an intravenous administration of DEX at 0.1 milligram per kilogram, a 10-fold lower dose of nanoDEX administered by inhalation produced even better effects against lung inflammation and injury in severe acute respiratory syndrome coronavirus 2-challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
|---|---|
| Enthalten in: |
Science advances - 9(2023), 24 vom: 16. Juni, Seite eadg3277 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Meng, Qian-Fang [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 16.06.2023 Date Revised 06.07.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1126/sciadv.adg3277 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM358167728 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM358167728 | ||
| 003 | DE-627 | ||
| 005 | 20231226074152.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1126/sciadv.adg3277 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1193.xml |
| 035 | |a (DE-627)NLM358167728 | ||
| 035 | |a (NLM)37315135 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Meng, Qian-Fang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.06.2023 | ||
| 500 | |a Date Revised 06.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines. The nanoDEX, made by encapsulating DEX with the iSEND, efficiently promoted the anti-inflammation effect of DEX in an acute pneumonia mouse model and suppressed DEX-induced bone density reduction in an osteoporosis rat model. Relative to an intravenous administration of DEX at 0.1 milligram per kilogram, a 10-fold lower dose of nanoDEX administered by inhalation produced even better effects against lung inflammation and injury in severe acute respiratory syndrome coronavirus 2-challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 700 | 1 | |a Tai, Wanbo |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Mingyao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Yuanwei |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Jialin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yangtao |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Zhiqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Guangyu |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Guang-Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Guocan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Rongchang |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Ningyi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Gong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaoyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Lang |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Science advances |d 2015 |g 9(2023), 24 vom: 16. Juni, Seite eadg3277 |w (DE-627)NLM247717614 |x 2375-2548 |7 nnns |
| 773 | 1 | 8 | |g volume:9 |g year:2023 |g number:24 |g day:16 |g month:06 |g pages:eadg3277 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1126/sciadv.adg3277 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 9 |j 2023 |e 24 |b 16 |c 06 |h eadg3277 | ||