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CM\u2010272, which is a novel epigenetic inhibitor of G9a, induces immunogenic cell death (ICD) for recovering the sensitivity to anti\u2010PD\u20101 antibodies; however, the efficacy of CM\u2010272 is greatly limited by promoting the transcription activity of HIF\u20101<jats:italic>\u03b1<\/jats:italic> to form a hypoxic environment. Here, a Fe<jats:sup>3+<\/jats:sup>\u2010based nanoscale metal\u2013organic framework (MIL\u201053) is used to load CM\u2010272 (ultra\u2010high loading rate of 56.4%) for realizing an MIL\u201053@CM\u2010272 nanoplatform. After entering bladder cancer cells, Fe<jats:sup>3+<\/jats:sup> not only promotes the decomposition of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> into O<jats:sub>2<\/jats:sub> for O<jats:sub>2<\/jats:sub>\u2010compensated sonodynamic therapy but reduces the high level of glutathione in the tumor microenvironment (TME) for enhancing reactive oxygen species, including ferroptosis and apoptosis. MIL\u201053 carriers can be degraded in response to the TME, accelerating the release of CM\u2010272, which helps achieve the maximum effectiveness in an O<jats:sub>2<\/jats:sub>\u2010sufficient TME by attenuating drug resistance. Furthermore, MIL\u201053@CM\u2010272 enhances dendritic cell maturation and synergistically combines it with an anti\u2010programmed cell death protein 1 antibody during the study of immune\u2010related pathways in the transcriptomes of bladder cancer cells using RNA\u2010seq. This study presents the first instance of amalgamating nanomedicine with CM\u2010272, inducing apoptosis, ferroptosis, and ICD to achieve the \u201cone arrow three eagle\u201d effect.<\/jats:p>","DOI":"10.1002\/adma.202310522","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T13:18:50Z","timestamp":1702041530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["A \u201cOne Arrow Three Eagle\u201d Strategy to Improve CM\u2010272 Primed Bladder Cancer Immunotherapy"],"prefix":"10.1002","volume":"36","author":[{"given":"Ruiqi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine  651 Dongfeng Road East Guangzhou 510060 P. R. 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