{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:04:18Z","timestamp":1789376658727,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"51","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L242126"],"award-info":[{"award-number":["L242126"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["PKU2024LCXQ018"],"award-info":[{"award-number":["PKU2024LCXQ018"]}],"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 Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tumor metabolic reprogramming plays a crucial role in cancer progression and therapeutic resistance. The competitive and compensatory relationship between glucose and lipid metabolism\u2014known as the Randle cycle\u2014poses a major challenge to single\u2010pathway metabolic inhibition strategies. In this study, we developed a glucose oxidase\u2010based nanogel (GOX\u2010NG) system using catechol\u2010functionalized alginate, which exhibits enhanced tumor penetration, prolonged retention, and sustained glucose depletion in the tumor microenvironment. When combined with etomoxir (ETX), a fatty acid oxidation (FAO) inhibitor, this system effectively implements dual metabolic suppression, thereby enhancing reactive oxygen species (ROS)\u2010induced immunogenic cell death and reprogramming the tumor immune microenvironment. Further combination with the immune checkpoint inhibitor \u03b1PD\u20101 amplified antitumor immune responses, achieving complete tumor regression in 60% of animals and full survival in 100% of tumor\u2010bearing mice. This strategy demonstrates significant potential in the treatment of metastatic tumors through a synergistic starvation\u2013oxidation\u2013immunotherapy loop and paves the way for applying intratumorally\u2010retaining nanogels to a broad spectrum of therapeutic proteins targeting metabolic pathways.<\/jats:p>","DOI":"10.1002\/advs.76109","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:08:56Z","timestamp":1781525336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal Targeting Randle Cycle and Immune Checkpoint for Potent Antitumor Therapy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-2158","authenticated-orcid":false,"given":"Yuan","family":"Gao","sequence":"first","affiliation":[{"name":"Central Laboratory NMPA Key Laboratory For Dental Materials National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Laboratory of Biomedical Materials Beijing Key Laboratory of Biomaterials for Oral Disease National Center For Stomatology National Clinical Research Center For Oral Diseases Peking University School and Hospital of Stomatology  Beijing P. R. China"},{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Gong","sequence":"additional","affiliation":[{"name":"Central Laboratory NMPA Key Laboratory For Dental Materials National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Laboratory of Biomedical Materials Beijing Key Laboratory of Biomaterials for Oral Disease National Center For Stomatology National Clinical Research Center For Oral Diseases Peking University School and Hospital of Stomatology  Beijing P. R. China"},{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Fu","sequence":"additional","affiliation":[{"name":"Central Laboratory NMPA Key Laboratory For Dental Materials National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Laboratory of Biomedical Materials Beijing Key Laboratory of Biomaterials for Oral Disease National Center For Stomatology National Clinical Research Center For Oral Diseases Peking University School and Hospital of Stomatology  Beijing P. R. China"},{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Central Laboratory NMPA Key Laboratory For Dental Materials National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Laboratory of Biomedical Materials Beijing Key Laboratory of Biomaterials for Oral Disease National Center For Stomatology National Clinical Research Center For Oral Diseases Peking University School and Hospital of Stomatology  Beijing P. R. China"},{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Sang","sequence":"additional","affiliation":[{"name":"Central Laboratory NMPA Key Laboratory For Dental Materials National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Laboratory of Biomedical Materials Beijing Key Laboratory of Biomaterials for Oral Disease National Center For Stomatology National Clinical Research Center For Oral Diseases Peking University School and Hospital of Stomatology  Beijing P. R. China"},{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binglin","family":"Chen","sequence":"additional","affiliation":[{"name":"Central Laboratory NMPA Key Laboratory For Dental Materials National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Laboratory of Biomedical Materials Beijing Key Laboratory of Biomaterials for Oral Disease National Center For Stomatology National Clinical Research Center For Oral Diseases Peking University School and Hospital of Stomatology  Beijing P. R. China"},{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinzhi","family":"Su","sequence":"additional","affiliation":[{"name":"Central Laboratory NMPA Key Laboratory For Dental Materials National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Laboratory of Biomedical Materials Beijing Key Laboratory of Biomaterials for Oral Disease National Center For Stomatology National Clinical Research Center For Oral Diseases Peking University School and Hospital of Stomatology  Beijing P. R. China"},{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine Translational Medicine Research Center &amp; Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices Naval Medical University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqi","family":"Wei","sequence":"additional","affiliation":[{"name":"First Clinical Division Peking University School and Hospital of Stomatology  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1838-6274","authenticated-orcid":false,"given":"Xuliang","family":"Deng","sequence":"additional","affiliation":[{"name":"Central Laboratory NMPA Key Laboratory For Dental Materials National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Laboratory of Biomedical Materials Beijing Key Laboratory of Biomaterials for Oral Disease National Center For Stomatology National Clinical Research Center For Oral Diseases Peking University School and Hospital of Stomatology  Beijing P. R. China"},{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"},{"name":"Department of Geriatric Dentistry Peking University School and Hospital of Stomatology  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Central Laboratory NMPA Key Laboratory For Dental Materials National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Laboratory of Biomedical Materials Beijing Key Laboratory of Biomaterials for Oral Disease National Center For Stomatology National Clinical Research Center For Oral Diseases Peking University School and Hospital of Stomatology  Beijing P. R. China"},{"name":"Institute of Advanced Clinical Medicine Peking University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010021\u201000378\u20106"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202213636"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.100036"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201606"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.05.005"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.08.006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217076"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010024\u201002205\u20106"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010026\u201001411\u20100"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.08.002"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.06.027"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(63)91500-9"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010025\u201001092\u20101"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010024\u201001047\u20102"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.01.029"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.2c00356"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bab.2165"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.202000110"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202208583"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.02.076"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201903895"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00247G"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010025\u201001924\u20101"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202400235"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat2784"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201800729"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010018\u20100262\u20106"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249\u2010020\u201001752\u20107"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6BM00434B"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010018\u20100384\u2010z"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115250"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24676-6"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202201734"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.113721"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/smtd.202300204"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010022\u201001267\u20102"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.06.001"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3366"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70178"},{"key":"e_1_2_11_41_1","first-page":"1329","article-title":"Fatty Acid Oxidation Is Dispensable for human Macrophage IL\u20104\u2010induced Polarization","volume":"1841","author":"Namgaladze D.","year":"2014","journal-title":"Biochimica et Biophysica Acta (BBA)\u2010Molecular and Cell Biology of Lipids"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2NR04693H"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.88"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.12.018"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00479H"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202310163"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.02.008"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202209765"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201029082\u20101"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201808325"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b06814"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e20407"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201902791"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2017.07.129"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2017.11.039"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics17020215"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.5b04645"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c10188"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202003708"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202403116"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202412843"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.79367"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.06.027"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(18)31999\u20108"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1604958"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76109","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.76109","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:23:31Z","timestamp":1789374211000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.76109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,15]]},"references-count":64,"journal-issue":{"issue":"51","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/advs.76109"],"URL":"https:\/\/doi.org\/10.1002\/advs.76109","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,15]]},"assertion":[{"value":"2026-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e76109"}}