{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:32:58Z","timestamp":1786447978994,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"40","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"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":["22474160"],"award-info":[{"award-number":["22474160"]}],"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":["22207130"],"award-info":[{"award-number":["22207130"]}],"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":["82503496"],"award-info":[{"award-number":["82503496"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA0912700"],"award-info":[{"award-number":["2022YFA0912700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2025A04J7148"],"award-info":[{"award-number":["2025A04J7148"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M763793"],"award-info":[{"award-number":["2024M763793"]}],"id":[{"id":"10.13039\/501100002858","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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Real\u2010time monitoring of kidney\u2010infiltrating cytotoxic T lymphocytes (CTLs) is crucial for evaluating immunotherapy in renal cell carcinoma (RCC). However, existing imaging probes often exhibit \u201calways\u2010on\u201d signals and poor renal clearance, limiting their ability to detect renal immune responses. Herein, we report renal\u2010clearable bio\u2010orthogonal near\u2010infrared (NIR) fluorogenic probes (BGRs) that specifically detect granzyme B (GzmB), a biomarker of CTL activation, for dynamic evaluation of RCC immunotherapy. BGRs are built on a nitrile\u2010substituted hemicyanine scaffold with a biothiol\u2010responsive cysteine tail that is dually locked with a GzmB\u2010responsive peptide and conjugated to renal clearable (2\u2010hydroxypropyl)\u2010\u03b2\u2010cyclodextrin (HP\u03b2CD). Following injection in RCC mouse models under immunotherapy, non\u2010fluorescent BGR\n                    <jats:sub>M<\/jats:sub>\n                    accumulates in the renal tumor, where dual cleavage by elevated glutathione (GSH) and GzmB releases HP\u03b2CD and exposes an aminothiol group, triggering nitrile\u2010aminothiol biorthogonal click reaction that activates NIR fluorescence and drives probe self\u2010assembly for enhanced imaging performance. BGRs not only differentiate immunotherapeutic responses in living mice but also enable sensitive optical urinalysis of GzmB in clinical specimens from RCC patients (n = 21), allowing precise stratification of immune activation before and after treatment. This work thus establishes a generalizable strategy for translational optical reporters that addresses the unmet clinical need for dynamic monitoring of immunotherapies in RCC and other urological cancers.\n                  <\/jats:p>","DOI":"10.1002\/advs.202524298","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T09:01:53Z","timestamp":1777021313000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioorthogonal Fluorogenic Reporters for Noninvasive Imaging and Urinalysis of Immunotherapeutic Response in Renal Cell Carcinoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Xingyue","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoshuai","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University Guangzhou China"},{"name":"Department of Pharmacy The Affiliated Dazu's Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangmin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Xiangya Hospital of Central South University Changsha China"},{"name":"Department of Urology The First Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiliang","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Stanford University School of Medicine Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Affiliated Dazu's Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Affiliated Dazu's Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4012-4406","authenticated-orcid":false,"given":"Jiaguo","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-022-00666-2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2021.102239"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-2372"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00473-4"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2848"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-022-00676-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000003557"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14061384"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2023.03.014"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01166-3"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.2020200070"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.716860"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2022.08.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c00659"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53197-2"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-3346"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.1c00529"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-022-00263-x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.125.269795"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.124.267529"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI161065"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2407"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29691-w"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri911"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3839"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202211409"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-023-01009-1"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-022-01224-2"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-019-0378-4"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c15387"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c15896"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-63311-7"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202313117"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55452-y"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202301696"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202306539"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202216142"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0358-7"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc2777"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.2c00142"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c08896"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201913314"},{"key":"e_1_2_8_44_1","article-title":"Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy","volume":"86","author":"Tracz A.","year":"2014","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.058566"},{"key":"e_1_2_8_46_1","article-title":"A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies","volume":"126","author":"Murphy K. A.","year":"2017","journal-title":"Journal of Visualized Experiments"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202524298","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202524298","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202524298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:50:57Z","timestamp":1786445457000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202524298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":45,"journal-issue":{"issue":"40","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/advs.202524298"],"URL":"https:\/\/doi.org\/10.1002\/advs.202524298","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"2025-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e24298"}}