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Benefiting from the homologous targeting effect of Renca cell membranes, the mCGYS\u2010LOx can be effectively internalized by Renca cells, open the \u201cgate\u201d, and then release LOx and copper (Cu) ions. LOx can catalyze excessive lactate in Renca cells into H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , following that the produced H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    is further converted by Cu ions to the highly toxic \u00b7OH, contributing to tumor CDT. Meanwhile, the excessive Cu ions effectively trigger tumor cuproptosis. These synergistic effects induce the release of damage associated molecular patterns (DAMPs) and activate immunogenic cell death (ICD), leading to DC maturation and infiltration of immune effector cells. Moreover, LOx\u2010mediated lactate consumption downregulates the expression of PD\u2010L1, crippling tumor immune escape. In addition, the mCGYL\u2010LOx improves T\n                    <jats:sub>1<\/jats:sub>\n                    \u2010weighted MRI signal, allowing for accurate diagnosis of ccRCC. This study demonstrates that the mCGYL\u2010LOx has great potential for improving therapy of ccRCC via the synergistic actions of CDT and cuproptosis as well as immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202400204","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T07:05:33Z","timestamp":1718003133000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Biomimetic Nano\u2010Regulator that Induces Cuproptosis and Lactate\u2010Depletion Mediated ROS Storm for Metalloimmunotherapy of Clear Cell Renal Cell Carcinoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaotong","family":"Xu","sequence":"first","affiliation":[{"name":"School of Pharmacy Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment Binzhou Medical University  Yantai 264003 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment Binzhou Medical University  Yantai 264003 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment Binzhou Medical University  Yantai 264003 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment Binzhou Medical University  Yantai 264003 P. R. 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