tetano
Editor, Senior Moderator
Sci Adv
. 2023 Jun 16;9(24):eadg3277.
doi: 10.1126/sciadv.adg3277. Epub 2023 Jun 14. Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates
Qian-Fang Meng[SUP] 1 [/SUP], Wanbo Tai[SUP] 2 3 [/SUP], Mingyao Tian[SUP] 4 [/SUP], Xinyu Zhuang[SUP] 4 [/SUP], Yuanwei Pan[SUP] 1 5 [/SUP], Jialin Lai[SUP] 1 [/SUP], Yangtao Xu[SUP] 1 [/SUP], Zhiqiang Xu[SUP] 4 [/SUP], Min Li[SUP] 6 [/SUP], Guangyu Zhao[SUP] 6 [/SUP], Guang-Tao Yu[SUP] 7 [/SUP], Guocan Yu[SUP] 8 [/SUP], Rongchang Chen[SUP] 9 [/SUP], Ningyi Jin[SUP] 4 [/SUP], Xiao Li[SUP] 4 [/SUP], Gong Cheng[SUP] 2 3 [/SUP], Xiaoyuan Chen[SUP] 5 10 11 12 [/SUP], Lang Rao[SUP] 1 [/SUP]
Affiliations
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.
. 2023 Jun 16;9(24):eadg3277.
doi: 10.1126/sciadv.adg3277. Epub 2023 Jun 14. Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates
Qian-Fang Meng[SUP] 1 [/SUP], Wanbo Tai[SUP] 2 3 [/SUP], Mingyao Tian[SUP] 4 [/SUP], Xinyu Zhuang[SUP] 4 [/SUP], Yuanwei Pan[SUP] 1 5 [/SUP], Jialin Lai[SUP] 1 [/SUP], Yangtao Xu[SUP] 1 [/SUP], Zhiqiang Xu[SUP] 4 [/SUP], Min Li[SUP] 6 [/SUP], Guangyu Zhao[SUP] 6 [/SUP], Guang-Tao Yu[SUP] 7 [/SUP], Guocan Yu[SUP] 8 [/SUP], Rongchang Chen[SUP] 9 [/SUP], Ningyi Jin[SUP] 4 [/SUP], Xiao Li[SUP] 4 [/SUP], Gong Cheng[SUP] 2 3 [/SUP], Xiaoyuan Chen[SUP] 5 10 11 12 [/SUP], Lang Rao[SUP] 1 [/SUP]
Affiliations
- PMID: 37315135
- DOI: 10.1126/sciadv.adg3277
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.