{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:23:15Z","timestamp":1791469395136,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"46","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"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":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chemoresistance remains a daunting challenge in bladder cancer therapy, primarily driven by cholesterol\u2010enriched rigid membranes that impede drug penetration and an immunosuppressive tumor microenvironment (TME) that evades immune surveillance. Herein, a biomimetic nanoplatform (DOX@COD\u2010ZCM@CS, DCZCMC) is reported engineered to orchestrate metabolic\u2010immunological crosstalk for synergistic reversal of chemoresistance. This integrated system comprises a Zn\u2010Co metal\u2010organic framework (Zn\u2010Co\u2010MOF, ZCM) core loaded with cholesterol oxidase (COD) and doxorubicin (DOX), surface\u2010functionalized with chondroitin sulfate (CS) for tumor\u2010specific targeting. Mechanistically, DCZCMC achieves three\u2010tiered synergism: 1) COD\u2010mediated cholesterol depletion (71.5% reduction, 111.2\u00a0vs 389.8 \u00b5\n                    <jats:sc>m<\/jats:sc>\n                    in the saline group) disrupts membrane rigidity, augmenting intratumoral drug retention to 87% (vs 39% with free DOX); 2) ZCM converts COD\u2010generated H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    into cytotoxic hydroxyl radicals (\u00b7OH), realizing pathological cholesterol\u2010to\u2010 reactive oxygen species (ROS) reprogramming for selective tumor oxidation; 3) Zn\n                    <jats:sup>2+<\/jats:sup>\n                    release triggers mitochondrial DNA (mtDNA) leakage, activating the cyclic GMP\u2010AMP synthase\u2010stimulator of interferon genes (cGAS\u2010STING) pathway to amplify interferon\u2010\u03b2 (IFN\u2010\u03b2) and High Mobility Group Protein 1 (HMGB1) secretion, thereby driving dendritic cells (DCs) maturation and adaptive immune activation. In drug\u2010resistant xenografts, DCZCMC exhibits exceptional antitumor efficacy (95.6% tumor suppression) without systemic toxicity. This self\u2010amplifying \u201cmetabolic priming\u2010immune activation\u201d cascade represents a paradigm shift in overcoming chemoresistance, offering a transformative strategy for bladder cancer and other malignancies characterized by metabolic\u2010immunological dysregulation.\n                  <\/jats:p>","DOI":"10.1002\/smll.202509075","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T13:01:26Z","timestamp":1759237286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Innovative DCZCMC Platform: Dual Regulation of Cholesterol Dynamics and the cGAS\/STING Pathway Activation to Combat Drug Resistance in Tumor Therapy"],"prefix":"10.1002","volume":"21","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of University of Science and Technology of China Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui 230001 China"},{"name":"Department of Medicine The First Affiliated Hospital of University of Science and Technology of China Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianchun","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of University of Science and Technology of China Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui 230001 China"},{"name":"Department of Surgery The Affiliated Hospital of Qingdao University  Qingdao 266003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery The Affiliated Hospital of Qingdao University  Qingdao 266003 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