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We identified that FL exhibits markedly low expression of NAD(P)H: quinone oxidoreductase 1 (NQO1), a key enzyme required for activating quinone\u2010based chemotherapeutics. To overcome this, we developed a novel therapeutic strategy that simultaneously upregulates NQO1 expression and provides its quinone substrate within tumor cells. This approach leverages the dual biological function of Cu\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    , which acts as both an inducer of NQO1 expression via the Nuclear factor erythroid 2\u2010related factor 2 (Nrf2) pathway and a catalyst for the oxidation of EGCG to its quinone form. Using a CD20\u2010targeted nanoplatform as a delivery tool, we achieved specific co\u2010delivery of EGCG and Cu\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    to follicular lymphoma cells. This strategy triggered a potent NQO1\u2010mediated redox cycle, resulting in severe NADH depletion and profound oxidative stress. These events activated the GADD45\u03b2\u2010MAPK stress\u2010signaling pathway, leading to mitochondrial dysfunction and apoptosis activation. In a murine FL xenograft model, this approach achieved 85% tumor growth inhibition, while maintaining a favorable safety profile. This work establishes a new therapeutic paradigm for FL, leveraging intrinsic enzyme deficiency to induce tumor\u2010specific, self\u2010amplifying cell death.\n                  <\/jats:p>","DOI":"10.1002\/advs.75538","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:54:47Z","timestamp":1778151287000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rewiring NADH Metabolism Through NQO1\u2010Mediated Redox Cycling for Targeted Follicular Lymphoma Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Jinxing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hematology School of Medicine The First Affiliated Hospital of Xiamen University and Institute of Hematology Xiamen University  Xiamen China"},{"name":"Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy and Xiamen Hematology Medical Quality Control Center  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