{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T01:29:39Z","timestamp":1781918979225,"version":"3.54.5"},"reference-count":87,"publisher":"Wiley","issue":"25","license":[{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303923"],"award-info":[{"award-number":["82303923"]}],"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":["82472087"],"award-info":[{"award-number":["82472087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2024J011004"],"award-info":[{"award-number":["2024J011004"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515013156"],"award-info":[{"award-number":["2024A1515013156"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2022YFC3401000"],"award-info":[{"award-number":["2022YFC3401000"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Immune checkpoint blockade (ICB) has emerged as a cornerstone of cancer therapy, yet its effectiveness remains restricted in PD\u2010L1\u2010low malignancies due to insufficient target expression. We herein develop the cuproptosis and disulfidptosis co\u2010delivery targeted (Cadict) nanodrug, an epidermal growth factor receptor (EGFR)\u2010targeted nanoplatform designed to co\u2010induce cuproptosis and disulfidptosis, thereby synergistically augmenting tumor cytotoxicity and sensitizing cancers to anti\u2010PD\u2010L1 therapy. Cadict exploits copper\u2010sulfur (Cu\u2010S) coordination chemistry to co\u2010deliver copper ions and cystine, while integrating glucose oxidase (GOx) to create a hypoglycemic milieu essential for disulfidptosis execution. This dual cytotoxic mechanism not only triggers immunogenic cell death\u2010like phenotype but also unexpectedly activates the integrated stress response (ISR), promoting PD\u2010L1 upregulation through Eif5b\u2010dependent translation. The resulting synergy between redox\u2010driven cytotoxicity and immune modulation potentiates anti\u2010PD\u2010L1 efficacy, leading to robust tumor regression and durable immunological memory. Our work presents a seminal strategy that leverages tumor redox vulnerabilities to advance cancer immunotherapy, providing a new paradigm for overcoming ICB resistance via targeted tumor sensitization.<\/jats:p>","DOI":"10.1002\/advs.202515367","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T17:37:29Z","timestamp":1771695449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cuproptosis and Disulfidptosis Converge to Empower PD\u2010L1 Checkpoint Therapy via Cadict\u2010Induced PD\u2010L1 Translation"],"prefix":"10.1002","volume":"13","author":[{"given":"Shaoqing","family":"Huang","sequence":"first","affiliation":[{"name":"Center for Gastrointestinal Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Center for Hepato\u2010Pancreatico\u2010Biliary Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialing","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine The First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihan","family":"Pu","sequence":"additional","affiliation":[{"name":"School of Public Health Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiatong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine The First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine The First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghai","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Hepato\u2010Pancreatico\u2010Biliary Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Department of General Surgery Hui Ya Hospital of The First Affiliated Hospital Sun Yat\u2010sen University  Huizhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-667X","authenticated-orcid":false,"given":"Mei","family":"Song","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Institute of Precision Medicine The First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4061-7382","authenticated-orcid":false,"given":"Weiling","family":"He","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Department of Gastrointestinal Surgery School of Medicine Xiang'an Hospital of Xiamen University Xiamen University  Xiamen Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2018.27"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.014"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adq3940"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015\u20100507"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.43"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(17)30512\u20100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2025.03.033"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010019\u20100919\u2010y"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201020\u20100471"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202212267"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.01.017"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202405639"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202403520"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202404971"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2007.01.003"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010021\u201000427\u20100"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010023\u201001091\u20102"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201039401\u20109"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1204338"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010023\u201003065\u20108"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c15932"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010025\u201001673\u20102"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202405494"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq3711"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202312169"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202204733"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c07555"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202311549"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202412227"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c14247"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122723"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202506126"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010025\u201001456\u20100"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201041121\u2010z"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk3201"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202309842"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202402516"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201053135\u20102"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202500337"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40820\u2010025\u201001828\u20108"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c00730"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2025.137611"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.03.052"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201009375\u2010y"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2018.1564568"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c13597"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202500908"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.76.9901"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b08714"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf0529"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13111888"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2015.01.007"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010physiol\u2010021014\u2010071649"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010physiol\u2010021119\u2010034627"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102891"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.105046"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1097\u20102765(00)00108\u20108"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010020\u20100056\u20100"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00792\u201011"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05033"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.74989"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010019\u20100126\u2010x"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2024.05.001"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0nh00674b"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103164"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.12.014"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010023\u201002720\u20102"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010025\u201003284\u20103"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202417616"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101434"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.05.016"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010020\u20100496\u2010x"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2010.07.003"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1134\/s0006297917100108"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18294"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aae0477"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.04.031"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.013"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.016"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25015"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010018\u20100161\u2010x"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2023.5343"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010025\u201003409\u20104"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010025\u201003186\u20104"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat5314"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010024\u201001434\u2010y"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201642195"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202515367","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202515367","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202515367","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T08:46:24Z","timestamp":1777884384000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202515367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,21]]},"references-count":87,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/advs.202515367"],"URL":"https:\/\/doi.org\/10.1002\/advs.202515367","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,21]]},"assertion":[{"value":"2025-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15367"}}