Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates

文献类型： 外文期刊

第一作者： Meng, Qian-Fang

作者： Meng, Qian-Fang;Pan, Yuanwei;Lai, Jialin;Xu, Yangtao;Rao, Lang;Tai, Wanbo;Cheng, Gong;Tai, Wanbo;Cheng, Gong;Tian, Mingyao;Zhuang, Xinyu;Xu, Zhiqiang;Jin, Ningyi;Li, Xiao;Pan, Yuanwei;Chen, Xiaoyuan;Pan, Yuanwei;Chen, Xiaoyuan;Pan, Yuanwei;Chen, Xiaoyuan;Pan, Yuanwei;Chen, Xiaoyuan;Pan, Yuanwei;Chen, Xiaoyuan;Li, Min;Zhao, Guangyu;Yu, Guang-Tao;Yu, Guocan;Chen, Rongchang;Chen, Xiaoyuan;Chen, Xiaoyuan;Chen, Xiaoyuan

作者机构：

期刊名称：SCIENCE ADVANCES （ 影响因子：13.6； 五年影响因子：15.4 ）

ISSN： 2375-2548

年卷期： 2023 年 9 卷 24 期

页码：

收录情况： SCI

摘要： 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.

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