{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:12:07Z","timestamp":1788970327904,"version":"build-2803163510"},"reference-count":66,"publisher":"American Chemical Society (ACS)","issue":"35","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2403203"],"award-info":[{"award-number":["2022YFC2403203"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52572303"],"award-info":[{"award-number":["52572303"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473773"],"award-info":[{"award-number":["82473773"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leading Talents in Shanghai in 2018"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nitric oxide (NO) holds promise for circumventing resistance to platinum-based chemotherapy by reprogramming the tumor microenvironment (TME) in lung adenocarcinoma (LUAD). However, their further application is greatly hindered by uncontrolled release kinetics and off-target toxicity. Herein, an inhalable NO nanogenerator (10m@FOMs-Cu) that reprograms the TME via specific NO release is developed by encapsulating a biorthogonal-activated NO-cisplatin prodrug into TME-responsive hybrid micelles, allowing for sustained and effective LUAD treatment. The prodrug integrates a Pt-based catalyst with a caged active NO donor within one molecule and is further encapsulated in a disulfide-cross-linked organosilica shell, enabling redox-triggered self-catalytic NO release while minimizing off-target injury to normal tissues. It is verified that nebulized 10m@FOMs-Cu could achieve efficient mucus-extracellular matrix dual barrier penetration to reach the TME, thereby ensuring sustained NO release to potentiate Pt(II)-mediated nuclear damage and Cu(II)\/Cu(I)-mediated cuproptosis. This sensitization process reprograms the TME by inducing metabolism-DNA stress feedback, triggering a systemic and durable immune response that confers efficient tumor suppression in orthotopic and rechallenged LUAD. It demonstrates that 10m@FOMs-Cu could serve as a potent and safe nebulized nanomedicine for LUAD therapy and provides insights into designing gas-based nanotherapeutics.<\/jats:p>","DOI":"10.1021\/jacs.6c13896","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:20:40Z","timestamp":1788351640000},"page":"38466-38482","source":"Crossref","is-referenced-by-count":0,"title":["An Inhalable Hybrid\nNitric Oxide Nanogenerator for\nLung Adenocarcinoma Treatment via Bioorthogonal-Activated Gas-Immunotherapy"],"prefix":"10.1021","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8447-4629","authenticated-orcid":true,"given":"Jinglin","family":"Zou","sequence":"first","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Leng","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6708-9833","authenticated-orcid":true,"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, P. R. China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, P. R. China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shi","sequence":"additional","affiliation":[{"name":"Shuguang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine , , ,","place":["Shanghai, China, 201203"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Shuguang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine , , ,","place":["Shanghai, China, 201203"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Tongji University School of Medicine , , ,","place":["Shanghai, China, 200092"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjiao","family":"Liu","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4222-6107","authenticated-orcid":true,"given":"Dapeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6409-8535","authenticated-orcid":true,"given":"Zhangjian","family":"Huang","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, P. R. China, 211198"]},{"name":"Xinjiang Medical University , , ,","place":["Urumqi, P. R. China, 830054"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-9528","authenticated-orcid":true,"given":"Yongsheng","family":"Li","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"2026090910102301900_cit1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics,\n2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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Oncol."},{"key":"2026090910102301900_cit4","doi-asserted-by":"publisher","first-page":"7265","DOI":"10.1038\/sj.onc.1206933","article-title":"Cisplatin:\nmode of cytotoxic action and molecular basis of resistance","volume":"22","author":"Siddik","year":"2003","journal-title":"Oncogene"},{"key":"2026090910102301900_cit5","doi-asserted-by":"publisher","first-page":"114173","DOI":"10.1016\/j.addr.2022.114173","article-title":"Nano-delivery to the lung - by inhalation or other\nroutes and why nano when micro is largely sufficient?","volume":"183","author":"Forest","year":"2022","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026090910102301900_cit6","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/s41571-025-01061-7","article-title":"Treatment of NSCLC after chemoimmunotherapy\n- are we making headway?","volume":"22","author":"Reck","year":"2025","journal-title":"Nat. Rev. Clin. 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Drug Delivery\nRev."},{"key":"2026090910102301900_cit30","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.jconrel.2023.11.014","article-title":"Strategies for gaseous\nneuromodulator release in chemical neuroscience: Experimental approaches\nand translational validation","volume":"365","author":"Ali","year":"2024","journal-title":"J. Controlled\nRelease"},{"key":"2026090910102301900_cit31","doi-asserted-by":"publisher","first-page":"216540","DOI":"10.1016\/j.ccr.2025.216540","article-title":"Harnessing stimuli-responsive NO nanomaterials for advanced multi-disease\ntherapy","volume":"533","author":"Zhang","year":"2025","journal-title":"Coord. Chem. Rev."},{"key":"2026090910102301900_cit32","doi-asserted-by":"publisher","first-page":"2312092","DOI":"10.1002\/adfm.202312092","article-title":"Nitric oxide-based\nnanomedicines for conquering TME fortress: Say \u201cNO\u201d\nto insufficient tumor treatment","volume":"34","author":"Xiang","year":"2024","journal-title":"Adv. Funct.\nMater."},{"key":"2026090910102301900_cit33","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202411260","article-title":"Spatiotemporal\nnitric oxide modulation via electrochemical platform to profile tumor\ncell response","volume":"63","author":"Won","year":"2024","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090910102301900_cit34","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.jconrel.2022.10.012","article-title":"Recent\nprogress in nitric oxide-generating nanomedicine for cancer therapy","volume":"352","author":"Li","year":"2022","journal-title":"J. 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Soc."},{"key":"2026090910102301900_cit38","doi-asserted-by":"publisher","first-page":"2503206","DOI":"10.1002\/adma.202503206","article-title":"Engineering\nred blood cells for amplified tumor dual-gas transfusion therapy","volume":"37","author":"Li","year":"2025","journal-title":"Adv. Mater."},{"key":"2026090910102301900_cit39","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202507388","article-title":"Ultrasound-responsive lipid nanosonosensitizers\nwith size reduction and NO release: Synergistic sonodynamic-chemo-immunotherapy\nfor pancreatic tumors","volume":"64","author":"Fang","year":"2025","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090910102301900_cit40","doi-asserted-by":"publisher","first-page":"2500242","DOI":"10.1002\/adma.202500242","article-title":"Artificial cells capable\nof NO generation with light\ncontrollable membraneless organelles for melanoma therapy","volume":"37","author":"Zhao","year":"2025","journal-title":"Adv. Mater."},{"key":"2026090910102301900_cit41","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202419939","article-title":"Intracellular co-delivery\nof carbon monoxide and nitric oxide induces mitochondrial apoptosis\nfor cancer therapy","volume":"64","author":"Shen","year":"2025","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090910102301900_cit42","doi-asserted-by":"publisher","first-page":"2415891","DOI":"10.1002\/adma.202415891","article-title":"Rational design\nof NIR-II fluorescence\/photoacoustic nanosensor tailored for mechanisms\nof diabetes-related breast cancer","volume":"37","author":"Zhang","year":"2025","journal-title":"Adv. Mater."},{"key":"2026090910102301900_cit43","doi-asserted-by":"publisher","first-page":"7941","DOI":"10.1021\/jacs.2c13218","article-title":"Highly sensitive imaging of tumor\nmetastasis based on the targeting and polarization of M2-like macrophages","volume":"145","author":"Yuan","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910102301900_cit44","doi-asserted-by":"publisher","first-page":"13899","DOI":"10.1021\/acs.jmedchem.0c01435","article-title":"General strategy for integrated bioorthogonal\nprodrugs: Pt(II)-Triggered depropargylation enables controllable drug\nactivation in vivo","volume":"63","author":"Sun","year":"2020","journal-title":"J. Med.\nChem."},{"key":"2026090910102301900_cit45","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1021\/acs.jmedchem.3c01693","article-title":"Development of integrated\nbioorthogonal self-catalyzed NO donor\/platinum(IV) prodrugs for synergistical\nintervention against triple-negative breast cancer","volume":"67","author":"Zhang","year":"2024","journal-title":"J. Med. Chem."},{"key":"2026090910102301900_cit46","doi-asserted-by":"publisher","first-page":"26726","DOI":"10.1021\/jacs.5c07409","article-title":"Warhead strategy for\ntargeted protein S-nitrosation","volume":"147","author":"Zhang","year":"2025","journal-title":"J. Am. Chem.\nSoc."},{"key":"2026090910102301900_cit47","doi-asserted-by":"publisher","first-page":"1704490","DOI":"10.1002\/adma.201704490","article-title":"Dual intratumoral redox\/enzyme-responsive\nNO-releasing nanomedicine\nfor the specific, high-efficacy, and low-toxic cancer therapy","volume":"30","author":"Jia","year":"2018","journal-title":"Adv. Mater."},{"key":"2026090910102301900_cit48","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/s41467-024-55658-0","article-title":"Tumor microenvironment-responsive\nengineered hybrid nanomedicine\nfor photodynamic-immunotherapy via multi-pronged amplification of\nreactive oxygen species","volume":"16","author":"Zou","year":"2025","journal-title":"Nat. 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