{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:10:10Z","timestamp":1790784610067,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"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":["82573681"],"award-info":[{"award-number":["82573681"]}],"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":["22377090"],"award-info":[{"award-number":["22377090"]}],"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":["82403319"],"award-info":[{"award-number":["82403319"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010882","name":"Tianjin Municipal Education Commission","doi-asserted-by":"publisher","award":["2025KJ001"],"award-info":[{"award-number":["2025KJ001"]}],"id":[{"id":"10.13039\/501100010882","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin Municipality","doi-asserted-by":"publisher","award":["23JCQNJC01120"],"award-info":[{"award-number":["23JCQNJC01120"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cisplatin (CDDP) chemosensitivity and severe toxicity severely limit its clinical application in muscle\u2010invasive bladder cancer (MIBC) and non\u2010muscle\u2010invasive bladder cancer (NMIBC). To address these unmet clinical needs, we synthesized a series of melatonin\u2010conjugated platinum(IV) prodrugs functionalized with isocyanate chains (compounds\n                    <jats:bold>5<\/jats:bold>\n                    \u2012\n                    <jats:bold>12<\/jats:bold>\n                    ), and identified MP\u201012C (compound\n                    <jats:bold>11<\/jats:bold>\n                    ) as the lead candidate with optimal potency and safety. In vitro assays showed that MP\u201012C exhibited far stronger antiproliferative activity than CDDP and mitomycin C in parental and CDDP\u2010resistant bladder cancer cells. Multiple in vivo models, including subcutaneous xenograft, orthotopic, and chemically induced spontaneous bladder cancer models, were adopted. Both intravenous injection and intravesical instillation of MP\u201012C achieved robust tumor suppression while reducing toxicity compared to conventional chemotherapeutics. Mechanistically, MP\u201012C downregulated the\n                    <jats:italic>TCF4\/COL6A3<\/jats:italic>\n                    axis to suppress collagen VI secretion by bladder cancer cells, thereby remodeling the extracellular matrix (ECM) and enhancing the sensitivity of bladder cancer cells to CDDP. MP\u201012C triggered immunogenic cell death and persistently activated the cGAS\u2010STING pathway, promoting dendritic cell maturation and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration to remodel the antitumor immune microenvironment. Collectively, MP\u201012C integrates ECM modulation and immune activation to exert superior anti\u2010bladder cancer efficacy with favorable safety, thus providing a promising platinum(IV) prodrug strategy for NMIBC and MIBC.\n                  <\/jats:p>","DOI":"10.1002\/advs.77833","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isocyanate\u2010Modified Melatplatin(IV) Enhances Antitumor Efficacy via TCF4\/COL6A3\u2010Mediated Extracellular Matrix Remodeling and cGAS\u2010STING Pathway Activation in Bladder Cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7932-0271","authenticated-orcid":false,"given":"Linhui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirun","family":"Su","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiping","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixuan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0306-2031","authenticated-orcid":false,"given":"Kaipeng","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuda","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6750-0934","authenticated-orcid":false,"given":"Zihan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3938-4190","authenticated-orcid":false,"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunkai","family":"Qie","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouliang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangkang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1660-412X","authenticated-orcid":false,"given":"Jingyuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8675-5524","authenticated-orcid":false,"given":"Hailong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010022\u201001517\u20109"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.03.055"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2022.08.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102022\u2010006551"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac545"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.103022"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfaf053"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.100938"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2025.08.014"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI145666"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3961\/jpmph.23.305"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44319\u2010023\u201000036\u2010y"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.95316"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787\u2010025\u201001751\u20109"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu17193120"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2024.01.010"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17809"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12158"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2023.2171158"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010022\u201001465\u2010y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano12071221"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201201344"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.02.041"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja5038269"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2015.12.006"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12288"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043353"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.72826"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.909811"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2021.100788"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.48699"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12071066"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115595"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010022\u201001008\u2010w"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010\u2010025\u201005329\u20107"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010025\u201003487\u20104"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202509075"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.08.065"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae973"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77833","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77833","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77833","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:48:42Z","timestamp":1790783322000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":39,"alternative-id":["10.1002\/advs.77833"],"URL":"https:\/\/doi.org\/10.1002\/advs.77833","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"2026-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77833"}}