{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:08:45Z","timestamp":1788930525569,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Stress\u2010generating therapeutic materials are commonly optimized to deliver cytotoxic inputs, but delivery alone does not determine whether intracellular stress becomes irreversible damage. Tumor cells can buffer metal\u2010, redox\u2010 and mitochondrial stress through glucose\u2010dependent metabolism, creating a gap between stress exposure and stress execution. Here, we report a tumor\u2010state\u2010gated metallo\u2010DNAzyme framework, C@HGDz\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>1<\/jats:sup>\n                    \/CaCu, that introduces metabolic licensing as a programmable material function. The framework couples a miR\u201021\/APE1\u2010gated GLUT1 DNAzyme with a Ca\/Cu\u2010partitioned metal\u2013nucleic\u2010acid architecture and co\u2010assembled cystine. Tumor\u2010state logic confines GLUT1 mRNA cleavage to dual\u2010input cancer\u2010associated conditions, whereas metal partitioning assigns Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    to DNAzyme\u2010compatible catalysis and Cu\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    to framework persistence and copper\u2010associated stress within the metabolically rewired cellular state. After HER2\u2010guided deployment, C@HGDz\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>1<\/jats:sup>\n                    \/CaCu suppresses GLUT1 and glycolytic signaling, restores PTEN\u2010associated signaling and remodels glucose\u2010derived metabolic buffering. This metabolic remodeling is associated with enhanced engagement of copper\u2010 and cystine\u2010dependent oxidative, mitochondrial and cytoskeletal stress. In an orthotopic gastric tumor model, the framework enhances tumor accumulation, shows coordinated metabolic rewiring and stress engagement, and suppresses tumor progression with apparent tolerability under the tested regimen. This work establishes state\u2010gated metallo\u2010DNAzyme framework engineering as a strategy for shifting stress\u2010generating materials from cytotoxic delivery to vulnerability programming.\n                  <\/jats:p>","DOI":"10.1002\/advs.77520","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:42:40Z","timestamp":1788928960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A State\u2010Gated Metallo\u2010DNAzyme Framework Programs Tumor Stress Vulnerability Through Metabolic Licensing"],"prefix":"10.1002","author":[{"given":"Xiaodong","family":"Ma","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Clinical Nutrition and Intervention The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Pharmaceutical Sciences Laboratory Faculty of Science and Engineering \u00c5bo Akademi University  Turku 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