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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\u2013challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases.<\/jats:p>","DOI":"10.1126\/sciadv.adg3277","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T13:57:40Z","timestamp":1686751060000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":111,"title":["Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1540-029X","authenticated-orcid":true,"given":"Qian-Fang","family":"Meng","sequence":"first","affiliation":[{"name":"Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, 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China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongchang","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Disease, Shenzhen People\u2019s Hospital, Shenzhen 518020, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1744-7402","authenticated-orcid":true,"given":"Ningyi","family":"Jin","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7866-3160","authenticated-orcid":true,"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, 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Medicine, National University of Singapore, Singapore 117597, Singapore."},{"name":"Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore."},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore 138673, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5010-0729","authenticated-orcid":true,"given":"Lang","family":"Rao","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, 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