{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:37:31Z","timestamp":1787243851716,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"39","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"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":["22177100and22277055"],"award-info":[{"award-number":["22177100and22277055"]}],"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":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The absence of precise targeting and defined mechanisms, akin to small molecules, remains a major barrier to the clinical translation of nanomedicines. Mammalian target of rapamycin complex 1 (mTORC1), a key regulator of cell proliferation and metabolism, is linked to abnormal activation in various diseases like cancers. While small\u2010molecule inhibitors of mTORC1 are limited, they remain a focus. Here, a strategy is presented for mTORC1\u2010specific nano\u2010inhibitors targeting the lysosomal arginine (Arg)\u2010SLC38A9\u2010mTORC1 pathway. Using [2Fe\u20102S]CO\n                    <jats:sub>6<\/jats:sub>\n                    as a universal paradigm, nanomedicines are developed (e.g., ZnPc\u2010SFeCO) that degrade Arg in the lysosome, inhibiting SLC38A9 activation and blocking mTORC1 recruitment. ZnPc\u2010SFeCO inhibits mTORC1 at ultra\u2010low concentrations (1.07 ng mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), with three orders of magnitude greater specificity than the clinical small molecule rapamycin. SLC38A9 knockout abolishes nanomedicine efficacy. Differential responses to the inhibitors are also observed in normal and bladder cancer cells, linked to SLC38A9 expression levels, suggesting potential for precise treatment of non\u2010muscle invasive bladder cancer (NMIBC). In vivo, ZnPc\u2010SFeCO combined with photodynamic therapy outperformed MMC in preventing tumor recurrence and extending survival. This work establishes a promising approach for developing mTORC1\u2010specific nano\u2010inhibitors with well\u2010defined targets and mechanisms, offering new insights into the development of precision nanomedicines for cancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.202504798","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T04:51:45Z","timestamp":1751604705000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["mTORC1 Selective Nano\u2010Inhibitor by Disrupting the Lysosomal Arginine\u2010SLC38A9\u2010 mTORC1\u2010CDKs Axis for Precision Bladder Cancer Therapy"],"prefix":"10.1002","volume":"37","author":[{"given":"Lulu","family":"Kong","sequence":"first","affiliation":[{"name":"National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaikai","family":"Xu","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlu","family":"Bao","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kebin","family":"Ye","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Fan","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Science Key Laboratory of High Performance Scientific Computation Xihua University  Chengdu 610039 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongming","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Urology Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School  Nanjing 210008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering Yancheng Institute of Technology  Yancheng 224051 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Wei","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3836-3782","authenticated-orcid":false,"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01523-7"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00641-8"},{"key":"e_1_2_9_1_3","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00416-y"},{"key":"e_1_2_9_1_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-023-00934-0"},{"key":"e_1_2_9_1_5","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00681-5"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114971"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01827-6"},{"key":"e_1_2_9_2_3","doi-asserted-by":"publisher","DOI":"10.1038\/nature17963"},{"key":"e_1_2_9_2_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2019.05.009"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11174-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00067"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00785-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03035-z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2019.09.001"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-00952-x"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-023-00138-1"},{"key":"e_1_2_9_8_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-0669-6"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1257132"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14107"},{"key":"e_1_2_9_9_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.046"},{"key":"e_1_2_9_9_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-020-0490-9"},{"key":"e_1_2_9_9_5","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-024-01271-0"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01072-8"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.4c00231"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c01872"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb1203-980"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-024-01824-w"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01226-w"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0024"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.187"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00405-8"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-024-00550-9"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00676-x"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag1417"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811727115"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-024-02054-0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-023-01411-5"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-0106-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00468-9"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-024-00914-7"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2024.06.005"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ic301647u"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03298"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200453961"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202504798","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.202504798","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202504798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:02:46Z","timestamp":1771394566000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202504798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,4]]},"references-count":44,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/adma.202504798"],"URL":"https:\/\/doi.org\/10.1002\/adma.202504798","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,4]]},"assertion":[{"value":"2025-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2504798"}}