{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:19:28Z","timestamp":1788373168840,"version":"build-2803163510"},"reference-count":44,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"36","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271223"],"award-info":[{"award-number":["82271223"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013105","name":"Shanghai Rising-Star Program","doi-asserted-by":"publisher","award":["24QB2706100"],"award-info":[{"award-number":["24QB2706100"]}],"id":[{"id":"10.13039\/501100013105","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Committee of Science and Technology for Program of Shanghai Academic\/Technology Research Leader","award":["TJBH08425107"],"award-info":[{"award-number":["TJBH08425107"]}]},{"name":"Hongkou District Health Commission","award":["Hongwei2401-03"],"award-info":[{"award-number":["Hongwei2401-03"]}]},{"name":"Hongkou District Health Commission","award":["HKLCYQ2024-02"],"award-info":[{"award-number":["HKLCYQ2024-02"]}]},{"name":"Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University","award":["SY-XKZT-2023-1001"],"award-info":[{"award-number":["SY-XKZT-2023-1001"]}]},{"name":"Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University","award":["SY-YKYTS-2024-1002"],"award-info":[{"award-number":["SY-YKYTS-2024-1002"]}]},{"name":"Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University","award":["sykyqd09501"],"award-info":[{"award-number":["sykyqd09501"]}]},{"name":"Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University","award":["SY-XKZI-2023-1009"],"award-info":[{"award-number":["SY-XKZI-2023-1009"]}]},{"name":"Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University","award":["sykyqd01902"],"award-info":[{"award-number":["sykyqd01902"]}]},{"name":"Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University","award":["SY-XKZT-2023-1004"],"award-info":[{"award-number":["SY-XKZT-2023-1004"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:p>Sepsis, a life-threatening syndrome driven by dysregulated host response to infection, is critically exacerbated by the uncontrolled formation of neutrophil extracellular traps (NETs), which amplify inflammation, promote microthrombosis, and precipitate multiple organ dysfunction. However, current therapeutic approaches remain inadequate in effectively targeting and modulating NETs, leaving a significant clinical gap in managing sepsis progression. Herein, we propose a \u201csequential NETs-clearance\u201d strategy to precisely mitigate NET-associated pathologies by simultaneously inhibiting NET overproduction and facilitating their targeted capture and degradation. We engineered a multifunctional metal-organic framework (MOF818) with intrinsic antioxidant activity, functionalized with a NETs-capturing poly(amidoamine) dendrimer and loaded with a NETs-degrading enzyme, micrococcal nuclease (MNase). This integrated platform efficiently scavenges excessive reactive oxygen species (ROS) to inhibit NETosis, while simultaneously capturing existing NETs via electrostatic interactions and enzymatically cleaving their DNA scaffold, thereby disrupting the self-sustaining inflammatory cascade. In vitro, this combinatorial treatment markedly reduced NET-mediated inflammatory responses, while treatment in murine models of sepsis significantly mitigated systemic cytokine storms, alleviated organ damage, and improved survival in septic mice. Importantly, this therapeutic efficacy was corroborated in ex vivo human specimens, where the nanocomposite significantly suppressed NETosis and reduced inflammatory cytokines in neutrophils and plasma derived from sepsis patients. This work establishes a versatile nanotherapeutic paradigm for multi-target modulation of NETs and oxidative stress, offering a promising translational avenue for the precise treatment of sepsis.<\/jats:p>","DOI":"10.1126\/sciadv.aef3930","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:59:26Z","timestamp":1788371966000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Sequential clearance of neutrophil extracellular traps for precision therapy of sepsis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9733-5366","authenticated-orcid":true,"given":"Nan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3281-9689","authenticated-orcid":true,"given":"Yuqin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2117-9719","authenticated-orcid":true,"given":"Miaomiao","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5652-600X","authenticated-orcid":true,"given":"Changwei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8566-4847","authenticated-orcid":true,"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7732-9969","authenticated-orcid":true,"given":"Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200434, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_3_2_3_2","first-page":"629","article-title":"Organ Dysfunction in Sepsis: An Ominous Trajectory From Infection To Death","volume":"92","author":"Caraballo C.","year":"2019","unstructured":"C. Caraballo, F. Jaimes, Organ Dysfunction in Sepsis: An Ominous Trajectory From Infection To Death. Yale J. Biol. Med. 92, 629\u2013640 (2019).","journal-title":"Yale J. Biol. Med."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuz004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jemermed.2012.07.084"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199206000-00002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200009001-00002"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2011.05.025"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-025-05283-0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.08.041"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23168953"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28492-5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1170"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.09.007"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adh5090"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26146563"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200606027"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0953-7"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.10.006"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01166-3"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering11111160"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07428-z"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.08.035"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-741298"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84538"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00491-3"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.07.005"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2024.11.028"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam8897"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909927107"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101413"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37952"},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"e02635","DOI":"10.1002\/adfm.202502635","article-title":"A responsive hydrogel containing bimetallic MOF enabling amplified ferroptosis for cancer therapy via dual cellular homeostasis disruption","volume":"36","author":"Wang M.","year":"2026","unstructured":"M. Wang, Q. Chen, Z. Cheng, Z. Dai, T. Wu, B. Han, F. Jia, C. Li, H. Chen, A responsive hydrogel containing bimetallic MOF enabling amplified ferroptosis for cancer therapy via dual cellular homeostasis disruption. Adv. Funct. Mater. 36, e02635 (2026).","journal-title":"Adv. Funct. Mater."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.83543"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202215244"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c09530"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c09663"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202401574"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202407758"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1607011113"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15541"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1254838"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay7148"},{"key":"e_1_3_2_45_2","first-page":"e1320009","article-title":"Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice","volume":"6","author":"Cedervall J.","year":"2017","unstructured":"J. Cedervall, A. Dragomir, F. Saupe, Y. Zhang, J. \u00c4rnl\u00f6v, E. Larsson, A. Dimberg, A. Larsson, A.-K. Olsson, Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice. Onco Targets Ther 6, e1320009 (2017).","journal-title":"Onco Targets Ther"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aef3930","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:01:15Z","timestamp":1788372075000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aef3930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":44,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2026,9,4]]}},"alternative-id":["10.1126\/sciadv.aef3930"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aef3930","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]},"assertion":[{"value":"2026-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaef3930"}}