{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:02:22Z","timestamp":1789567342739,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) therapy is severely constrained by the immunosuppressive tumor microenvironment (TME). This study presents a TME\u2010responsive nanometabolic regulator, ZnO\n                    <jats:sub>2<\/jats:sub>\n                    @Fe@HA (ZFH), designed to bridge mitochondrial dysfunction, lipid reprogramming, and ferroptosis to enhance anti\u2010tumor immunity. ZFH specifically dissociates in the acidic TME, releasing Zn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    , Fe\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    , and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    . Crucially, ZFH leverages Zn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    to trigger mitochondrial oxidative stress and mitophagy, which subsequently disrupts the mitochondrial fatty acid \u03b2\u2010oxidation pathway. This mitochondria\u2010driven metabolic reprogramming causes a substantial accumulation of intracellular free fatty acids, effectively providing abundant lipid substrates to fuel iron\u2010catalyzed lipid peroxidation. This cascade successfully overcomes the lipid deficiency bottleneck of conventional ferroptosis. The resulting intense ferroptosis induces potent immunogenic cell death (ICD), facilitating dendritic cell maturation and effector T cell infiltration. In vitro and in vivo results demonstrate that ZFH effectively suppresses CRC growth via this mitochondria\u2010lipid\u2010ferroptosis axis. This mechanism\u2010guided strategy offers a promising paradigm for treating refractory CRC.\n                  <\/jats:p>","DOI":"10.1002\/smll.75825","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:03:22Z","timestamp":1789563802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Breaking the Lipid Bottleneck: A Mitophagy\u2010Driven Nanoregulator Amplifies Ferroptosis for Colorectal Cancer Immunotherapy"],"prefix":"10.1002","author":[{"given":"Shaopeng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery Harbin Medical University Cancer Hospital  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of General Surgery Qilu Hospital Shandong University  Jinan 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