{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:08:30Z","timestamp":1791284910953,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52073219"],"award-info":[{"award-number":["52073219"]}],"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":["52373304"],"award-info":[{"award-number":["52373304"]}],"id":[{"id":"10.13039\/501100001809","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":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inhibition of glutamine metabolism in tumor cells can cause metabolic compensation\u2010mediated glycolysis enhancement and PD\u2010L1 upregulation\u2010induced immune evasion, significantly limiting the therapeutic efficacy of glutamine inhibitors. Here, inspired by the specific binding of receptor and ligand, a PD\u2010L1\u2010targeting metabolism and immune regulator (PMIR) are constructed by decorating the glutaminase inhibitor (BPTES)\u2010loading zeolitic imidazolate framework (ZIF) with PD\u2010L1\u2010targeting peptides for regulating the metabolism within the tumor microenvironment (TME) to improve immunotherapy. At tumor sites, PMIR inhibits glutamine metabolism of tumor cells for elevating glutamine levels within the TME to improve the function of immune cells. Ingeniously, the accompanying PD\u2010L1 upregulation on tumor cells causes self\u2010amplifying accumulation of PMIR through PD\u2010L1 targeting, while also blocking PD\u2010L1, which has the effects of converting enemies into friends. Meanwhile, PMIR exactly offsets the compensatory glycolysis, while disrupting the redox homeostasis in tumor cells via the cooperation of components of the ZIF and BPTES. These together cause immunogenic cell death of tumor cells and relieve PD\u2010L1\u2010mediated immune evasion, further reshaping the immunosuppressive TME and evoking robust immune responses to effectively suppress bilateral tumor progression and metastasis. This work proposes a rational strategy to surmount the obstacles in glutamine inhibition for boosting existing clinical treatments.<\/jats:p>","DOI":"10.1002\/adma.202309094","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T11:01:50Z","timestamp":1701169310000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["A PD\u2010L1\u2010targeting Regulator for Metabolic Reprogramming to Enhance Glutamine Inhibition\u2010Mediated Synergistic Antitumor Metabolic and Immune Therapy"],"prefix":"10.1002","volume":"36","author":[{"given":"Xiao\u2010Kang","family":"Jin","sequence":"first","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Man","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Long","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun\u2010Kang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You\u2010Teng","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian\u2010Xiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9543-7763","authenticated-orcid":false,"given":"Chuan\u2010Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian\u2010Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0140-9"},{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.71"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2022.09.007"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2021.04.003"},{"key":"e_1_2_7_2_3","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.2c00111"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c02605"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.10.001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903586"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.06.010"},{"key":"e_1_2_7_4_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06299-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.2c02475"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-021-01316-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1611406113"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03442-1"},{"key":"e_1_2_7_6_3","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202003732"},{"key":"e_1_2_7_6_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0406-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.10.015"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.4501"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2022.101987"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mattod.2023.06.024"},{"key":"e_1_2_7_9_3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.2c05029"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202103534"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611376200"},{"key":"e_1_2_7_10_3","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat1022"},{"key":"e_1_2_7_10_4","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201902714"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2022.134781"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2018.12.016"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202205924"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202105783"},{"key":"e_1_2_7_12_3","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202200389"},{"key":"e_1_2_7_12_4","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202008858"},{"key":"e_1_2_7_12_5","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202001452"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.1c13304"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c03587"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202103015"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202103015"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202106654"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo5285"},{"key":"e_1_2_7_16_3","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202111784"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3MH00748K"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-018-0319-4"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.06.032"},{"key":"e_1_2_7_18_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2023.02.027"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01050-0"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202007630"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2021.05.135"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202309094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T22:00:43Z","timestamp":1759788043000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202309094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,6]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/adma.202309094"],"URL":"https:\/\/doi.org\/10.1002\/adma.202309094","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,6]]},"assertion":[{"value":"2023-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2309094"}}