{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T07:07:23Z","timestamp":1783840043153,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"33","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFA1212100"],"award-info":[{"award-number":["2024YFA1212100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFA0918600"],"award-info":[{"award-number":["2024YFA0918600"]}],"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":["32571631"],"award-info":[{"award-number":["32571631"]}],"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":["82572394"],"award-info":[{"award-number":["82572394"]}],"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":["82402452"],"award-info":[{"award-number":["82402452"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2025ZYGXZR059"],"award-info":[{"award-number":["2025ZYGXZR059"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cholestatic hepatitis is a progressive inflammatory liver disease characterized by disrupted bile acid homeostasis, excessive reactive oxygen species (ROS) generation, and chronic inflammation, remains clinically challenging due to limited diagnostic precision and lack of effective, targeted therapies. Here, we developed a multifunctional theranostic nanoplatform, CyP\u2010CuGA\u2010UDCA nanosheets (NSs), that integrates therapeutic intervention with enzyme\u2010responsive disease monitoring. The platform features copper\u2010gallic acid (CuGA) nanozymes with superoxide dismutase\u2010, peroxidase\u2010, and catalase\u2010like activities for effective ROS scavenging and NLRP3 inflammasome inhibition. Co\u2010loaded with ursodeoxycholic acid (UDCA) to alleviate bile acid toxicity, and with an alkaline phosphatase (ALP)\u2010responsive near\u2010infrared fluorescent probe (CyP), the nanoplatform enables targeted treatment and real\u2010time imaging of cholestatic lesions. In a DDC\u2010induced mice model, CyP\u2010CuGA\u2010UDCA NSs significantly suppressed pro\u2010inflammatory cytokine production, reduced hepatic macrophage infiltration, attenuated oxidative stress and hepatocyte apoptosis, and alleviated fibrosis, outperforming monotherapies. Concurrently, the ALP\u2010activated fluorescence allowed precise visualization of cholestatic progression in vivo. This study presents a first\u2010in\u2010class nanostructured system that couples NLRP3 inflammasome modulation and bile acid regulation with enzyme\u2010specific diagnostics, offering a robust strategy for precision therapy and monitoring of cholestatic hepatitis.<\/jats:p>","DOI":"10.1002\/adma.73312","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:24:47Z","timestamp":1778570687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ALP\u2010Responsive Luminescent Nanosheets Promote Precise Hepatitis Theragnostic by Co\u2010Targeting NLRP3 and Cholestasis"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5254-3551","authenticated-orcid":false,"given":"Jieying","family":"Qian","sequence":"first","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianwu","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoxu","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youpei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Du","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowan","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7452-2467","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6465-7488","authenticated-orcid":false,"given":"Yunjiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong P. R. China"},{"name":"National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Engineering of Guangdong Province South China University of Technology Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010019\u20100226\u20107"},{"key":"e_1_2_9_3_1","first-page":"1267","article-title":"Current Therapeutics in Primary Sclerosing Cholangitis","volume":"11","author":"Tan N.","year":"2023","journal-title":"Journal of Clinical and Translational Hepatology"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.08.013"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929\u2010024\u201001052\u20103"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(18)30300\u20103"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102618"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01182.2005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3727\/105221619X15614873062730"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.040"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3893"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010019\u20100165\u20100"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3806"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.97"},{"key":"e_1_2_9_15_1","first-page":"246","article-title":"Alkaline Phosphatase Normalization Is a Biomarker of Improved Survival in Primary Sclerosing Cholangitis","volume":"15","author":"Hilscher M.","year":"2016","journal-title":"Annals of Hepatology"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2023.117335"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202314039"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c00731"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2024.126475"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201036469\u20101"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202001675"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202301346"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010biochem\u2010061516\u2010045037"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202214693"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201016544\u20107"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b12070"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500310b"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202405937"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109\u2010020\u201002032\u20104"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2019.12.008"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.58"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.104"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.10.027"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.057"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608083200"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000485089"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1831"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.2.367"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2016.1103735"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201032575\u20108"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010024\u201001687\u2010w"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.73312","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.73312","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.73312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T06:10:31Z","timestamp":1783836631000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.73312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":40,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/adma.73312"],"URL":"https:\/\/doi.org\/10.1002\/adma.73312","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]},"assertion":[{"value":"2025-12-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e73312"}}