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

作者：Qian‐Fang Meng, Wanbo Tai, Mingyao Tian, Xinyu Zhuang, Yuanwei Pan, Jialin Lai, Yangtao Xu, Zhiqiang Xu, Min Li, Guangyu Zhao, Guang‐Tao Yu, Guocan Yu, Rongchang Chen, Ningyi Jin, Xiao Li, Gong Cheng, Xiaoyuan Chen, Lang Rao · 发表于：Science Advances · 年份：2023 · DOI：10.1126/sciadv.adg3277 · 被引用次数：110 · 研究领域：Extracellular vesicles in disease、Nanoplatforms for cancer theranostics、Immune cells in cancer

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.