{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:04:48Z","timestamp":1791813888784,"version":"4.3.4"},"reference-count":76,"publisher":"Wiley","issue":"29","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["202006380061"],"award-info":[{"award-number":["202006380061"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR JCJC NANOSEPSIS"],"award-info":[{"award-number":["ANR JCJC NANOSEPSIS"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study investigates the potential of pulmonary delivery of siRNA as an emergency therapy for acute lung injury (ALI). To obtain a quick anti\u2010inflammatory response, TNF\u2010\u03b1, a critical pro\u2010inflammatory cytokine, is knocked down for its early involvement in inflammatory responses. Therefore, TNF\u2010\u03b1 siRNA\u2010lipid nanoparticles (LNPs) are designed and characterized for cellular uptake in lipopolysaccharide (LPS)\u2010activated RAW264.7 murine macrophages, primary alveolar macrophages, and neutrophils from a murine ALI model. Intracellular trafficking and siRNA cytoplasmic release are evaluated in untreated and LPS\u2010activated RAW264.7 cells. LPS\u2010activated cells exhibit a fast and strong uptake of LNPs, including in primary cells. In RAW264.7 cells, significant endosomal escape and siRNA cytoplasmic release are observed after 16 h.\n                    <jats:italic>In vit<\/jats:italic>\n                    ro efficacy studies reveal consistent TNF\u2010\u03b1 inhibition across pre\u2010, co\u2010, and post\u2010incubation protocols, confirming the versatility of siRNA\u2010LNPs in preventive or curative conditions. After intratracheal administration of TNF\u2010\u03b1 siRNA\u2010LNPs in a murine ALI model, the distribution of LNPs demonstrates an accumulation in immune cells, including macrophages and neutrophils, reducing TNF\u2010\u03b1 and IL\u20106 levels, indicating a rapid anti\u2010inflammatory effect. This work underscores the efficacy of TNF\u2010\u03b1 siRNA\u2010LNPs in treating lung inflammatory diseases like ALI and highlights the importance of optimizing LNP distribution and delivery timing to enhance therapeutic outcomes.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202500695","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T05:40:14Z","timestamp":1754631614000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pulmonary Delivery of siRNA Anti\u2010TNF\u03b1\u2010loaded Lipid Nanoparticles for Rapid Recovery in Murine Acute Lung Injury"],"prefix":"10.1002","volume":"14","author":[{"given":"Qinglin","family":"Wang","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay CNRS Institut Galien Paris\u2010Saclay  Orsay 91400 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihana","family":"Achour","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay CNRS Institut Galien Paris\u2010Saclay  Orsay 91400 France"},{"name":"IHU\u2010SEPSIS Comprehensive Sepsis Center Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Emam","sequence":"additional","affiliation":[{"name":"IHU\u2010SEPSIS Comprehensive Sepsis Center Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"},{"name":"General Intensive Care Unit Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"},{"name":"Universit\u00e9 Paris\u2010Saclay UVSQ INSERM  U1173 2I Montigny\u2010le\u2010Bretonneux 78180 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younes","family":"Louaguenouni","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay CNRS Institut Galien Paris\u2010Saclay  Orsay 91400 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Cailleau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay CNRS Institut Galien Paris\u2010Saclay  Orsay 91400 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Mercier\u2010Nom\u00e9","sequence":"additional","affiliation":[{"name":"UMS\u2010IPSIT Plateforme PHIC Universit\u00e9 Paris\u2010Saclay CNRS Inserm Ing\u00e9nierie et Plateformes au Service de l'Innovation Th\u00e9rapeutique  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5997-2694","authenticated-orcid":false,"given":"S\u00e9verine","family":"Domenichini","sequence":"additional","affiliation":[{"name":"UMS\u2010IPSIT Plateforme MIPSIT Universit\u00e9 Paris\u2010Saclay CNRS Inserm Ing\u00e9nierie et Plateformes au Service de l'Innovation Th\u00e9rapeutique  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Delomenie","sequence":"additional","affiliation":[{"name":"UMS\u2010IPSIT Plateforme ACTAGEN Universit\u00e9 Paris\u2010Saclay CNRS Inserm Ing\u00e9nierie et Plateformes au Service de l'Innovation Th\u00e9rapeutique  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sezen","family":"Gul","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay CNRS Institut Galien Paris\u2010Saclay  Orsay 91400 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2417-9490","authenticated-orcid":false,"given":"Juliette","family":"Vergnaud","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay CNRS Institut Galien Paris\u2010Saclay  Orsay 91400 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-2626","authenticated-orcid":false,"given":"Nicolas","family":"Tsapis","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay CNRS Institut Galien Paris\u2010Saclay  Orsay 91400 France"},{"name":"IHU\u2010SEPSIS Comprehensive Sepsis Center Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Mansart","sequence":"additional","affiliation":[{"name":"IHU\u2010SEPSIS Comprehensive Sepsis Center Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"},{"name":"General Intensive Care Unit Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"},{"name":"Universit\u00e9 Paris\u2010Saclay UVSQ INSERM  U1173 2I Montigny\u2010le\u2010Bretonneux 78180 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6805-8944","authenticated-orcid":false,"given":"Djillali","family":"Annane","sequence":"additional","affiliation":[{"name":"IHU\u2010SEPSIS Comprehensive Sepsis Center Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"},{"name":"General Intensive Care Unit Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"},{"name":"Universit\u00e9 Paris\u2010Saclay UVSQ INSERM  U1173 2I Montigny\u2010le\u2010Bretonneux 78180 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7405-5600","authenticated-orcid":false,"given":"Francois","family":"Fay","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay CNRS Institut Galien Paris\u2010Saclay  Orsay 91400 France"},{"name":"IHU\u2010SEPSIS Comprehensive Sepsis Center Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"},{"name":"Institut Universitaire de France (IUF)  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3194-961X","authenticated-orcid":false,"given":"Elias","family":"Fattal","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay CNRS Institut Galien Paris\u2010Saclay  Orsay 91400 France"},{"name":"IHU\u2010SEPSIS Comprehensive Sepsis Center Raymond Poincar\u00e9 Hospital (AP\u2010HP) University of Versailles Saint\u2010Quentin en Yvelines University Paris Saclay  Garches 92380 France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"1","volume":"10","author":"Sun B.","year":"2023","journal-title":"Front. Med."},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2011.00065"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-023-04727-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00792-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/BTT.S207246"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta15suppl1-01"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00797-2"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03520360048038"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.3.9810012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.12.004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-019-1308-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.05.019"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.220"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21876"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.10.026"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-008-0131-3"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.2c01117"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2020.08.009"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2014.05.018"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.7b00572"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NR01928B"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2021.100424"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c05647"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2021.100424"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.03.013"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.02.017"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2612"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-014-1366-7"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-52685-1"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986709788803024"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3010"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.12.010"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.11.002"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120498"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.07.019"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.133.2.913"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.2MR0316-117RR"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.00899.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-021-00812-0"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2011.12.007"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2014.06.038"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00707F"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2614"},{"key":"e_1_2_8_44_1","first-page":"1","volume":"120","author":"Zheng L.","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2307800120"},{"key":"e_1_2_8_46_1","first-page":"3656","volume":"7","author":"Chou H. C.","year":"2024","journal-title":"Nano Mater"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade1444"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.04.004"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03127-z"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.06.001"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.27"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2007.01.003"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.183"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1989"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07774"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2014.875524"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2008.06.008"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2024.114222"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103479"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.12.027"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2023.103049"},{"key":"e_1_2_8_62_1","first-page":"1","volume":"8","author":"Meng Z.","year":"2017","journal-title":"Front. Immunol."},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.07.001"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-01184-w"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.1c00704"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2015.06.006"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS01127D"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-00858-8"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01452-1"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.10.006"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2024.01.032"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0366MA"},{"key":"e_1_2_8_73_1","first-page":"1","volume":"2017","author":"Hoecke L.","year":"2017","journal-title":"J. Vis. Exp."},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01066"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.04.002"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.17.4.320"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202500695","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T10:38:24Z","timestamp":1763116704000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202500695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,7]]},"references-count":76,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/adhm.202500695"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202500695","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,7]]},"assertion":[{"value":"2025-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00695"}}