{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:50:47Z","timestamp":1791273047155,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018532","name":"Major Scientific and Technological Innovation Project of Shandong Province","doi-asserted-by":"publisher","award":["2025ZLGX04"],"award-info":[{"award-number":["2025ZLGX04"]}],"id":[{"id":"10.13039\/501100018532","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021QH081"],"award-info":[{"award-number":["ZR2021QH081"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lactate, as a key metabolite in the tumor microenvironment (TME), has been reported to inhibit the stimulator of interferon genes (STING) pathway and contribute to immunosuppression and tumor progression. Here, we develop a dual\u2010enzyme delivery system (Fuc@ZIF\u2010GOx\u2010LOx, FZGL) that is coated with fucoidan (Fuc) and loaded with glucose oxidase (GOx) and lactate oxidase (LOx) based on zinc imidazolate framework\u201090 (ZIF\u201090), to inhibit breast cancer metastasis by \u201csource interception and downstream blockade\u201d of lactate. FZGL targets tumor cells via Fuc and releases GOx and LOx by the ATP\u2010responsive degradation of ZIF\u201090. GOx rapidly consumes glucose to block lactate generation from the source (\u201csource interception\u201d) and induces disulfidptosis in tumor cells. LOx degrades accumulated lactate (\u201cdownstream blockade\u201d) to alleviate immunosuppression. FZGL activates the cGAS\u2010STING pathway by damaging mitochondria and inducing mitochondrial DNA (mtDNA) release. Furthermore, lactate depletion can relieve lactate\u2010mediated inhibition of STING signaling, thereby enhancing the anti\u2010tumor immune response. In vivo experiments demonstrate that FZGL significantly promotes T cell infiltration and M1 macrophage polarization, and effectively inhibits the growth and lung metastasis of breast cancer. Our study provides a new approach for metastatic breast cancer treatment through lactate metabolism intervention.<\/jats:p>","DOI":"10.1002\/adhm.71801","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:54:46Z","timestamp":1791269686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Dual\u2010Enzyme Delivery System Targeting Lactate Depletion to Induce Disulfidptosis and Activate STING Pathway for Inhibiting Breast Cancer Metastasis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6379-8683","authenticated-orcid":false,"given":"Lianxiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1685-1750","authenticated-orcid":false,"given":"Jianhui","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinli","family":"Pang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijie","family":"Diao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5843-8596","authenticated-orcid":false,"given":"Yanguo","family":"Su","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2479-6977","authenticated-orcid":false,"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4303-8768","authenticated-orcid":false,"given":"Tianze","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9167-0840","authenticated-orcid":false,"given":"Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy Ocean University of China  Qingdao China"},{"name":"Laboratory For Marine Drugs and Bioproducts Qingdao Marine Science and Technology Center  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010020\u201001161\u20104"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010024\u201001990\u20104"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202422502"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.04.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007620\u20109"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u201003045\u20102"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi8602"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2022.10.006"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007992\u2010y"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202503733"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.10.037"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202502221"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2024.154378"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202410957"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202309842"},{"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\u2010024\u201053135\u20102"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202413095"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202411247"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c14609"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202313029"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202304845"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202415120"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202414121"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.114593"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2025.138612"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.5c00156"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3NR02026F"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2023.342111"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/bios11070208"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b01229"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c00730"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.114181"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202403253"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113244"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2024.102764"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202401328"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202409378"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122696"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201055751\u20104"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2023.144067"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.71801","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.71801","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.71801","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:54:47Z","timestamp":1791269687000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.71801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":42,"alternative-id":["10.1002\/adhm.71801"],"URL":"https:\/\/doi.org\/10.1002\/adhm.71801","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"assertion":[{"value":"2026-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71801"}}