{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:05:48Z","timestamp":1790345148039,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"54","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mitochondria\u2010targeted photodynamic immunotherapy has emerged as a promising strategy that combines organelle\u2010specific delivery with immunomodulation for cancer treatment. However, inadequate photosensitizer efficiency and insufficient targeting often limit its therapeutic efficacy. To systematically address these limitations, we developed a ZIF\u201090\u2010based immunomodulatory prodrug exhibiting mitochondria\u2010associated accumulation that enables tumor therapy by synergistically integrating metal ion interference with in situ photoimmunotherapy. This prodrug undergoes disassembly in the high\u2010ATP tumor microenvironment, releasing metal ions (Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , Mn\n                    <jats:sup>2+<\/jats:sup>\n                    ), and 5\u2010aminolevulinic acid (5\u2010ALA). 5\u2010ALA is metabolized via the heme biosynthesis pathway to generate photoactive protoporphyrin IX (PpIX) within mitochondria. A detailed molecular docking and mechanistic study reveals that Zn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    potently inhibits ferrochelatase (FECH) by displacing its native Fe\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    cofactor, thereby blocking PpIX\u2010to\u2010heme conversion and enabling unprecedented photosensitizer retention at the target site. The co\u2010released Zn\n                    <jats:sup>2+<\/jats:sup>\n                    \/Mn\n                    <jats:sup>2+<\/jats:sup>\n                    ions further disrupt mitochondrial complexes I\/II, resulted in electron transport chain collapse and amplified oxidative stress. Concurrently, Mn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    release was associated with cGAS\u2010STING\u2010related immune signaling and enhanced antitumor immune responses. This work demonstrates mitochondrial ion interference as a therapeutic cascade to enhance photoimmunotherapy, overcoming the limitations of traditional photodynamic therapy and immunosuppressive tumor microenvironments.\n                  <\/jats:p>","DOI":"10.1002\/smll.74881","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:41:09Z","timestamp":1785490869000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cascade Amplification of Photoimmunotherapy via Mitochondrial Dual\u2010Ion Interference in a Bimetallic\u2010Organic Framework"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9306-2080","authenticated-orcid":false,"given":"Zhiyue","family":"Cao","sequence":"first","affiliation":[{"name":"School of Medicine and Health Zhengzhou Advanced Research Institute Key Laboratory of Micro\u2010systems and Micro\u2010structures Manufacturing (Ministry of Education) Harbin Institute of Technology Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9421-2067","authenticated-orcid":false,"given":"Jia","family":"Jiao","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Zhengzhou Advanced Research Institute Key Laboratory of Micro\u2010systems and Micro\u2010structures Manufacturing (Ministry of Education) Harbin Institute of Technology Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghui","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Zhengzhou Advanced Research Institute Key Laboratory of Micro\u2010systems and Micro\u2010structures Manufacturing (Ministry of Education) Harbin Institute of Technology Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyu","family":"Su","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Zhengzhou Advanced Research Institute Key Laboratory of Micro\u2010systems and Micro\u2010structures Manufacturing (Ministry of Education) Harbin Institute of Technology Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaiyang","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Zhengzhou Advanced Research Institute Key Laboratory of Micro\u2010systems and Micro\u2010structures Manufacturing (Ministry of Education) Harbin Institute of Technology Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5595-9011","authenticated-orcid":false,"given":"Renkai","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Zhengzhou Advanced Research Institute Key Laboratory of Micro\u2010systems and Micro\u2010structures Manufacturing (Ministry of Education) Harbin Institute of Technology Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6479-1070","authenticated-orcid":false,"given":"Rui","family":"Xin","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Zhengzhou Advanced Research Institute Key Laboratory of Micro\u2010systems and Micro\u2010structures Manufacturing (Ministry of Education) Harbin Institute of Technology Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2466-6164","authenticated-orcid":false,"given":"Qiuyue","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Zhengzhou Advanced Research Institute Key Laboratory of Micro\u2010systems and Micro\u2010structures Manufacturing (Ministry of Education) Harbin Institute of Technology Harbin 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