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Multimodal synergistic therapy has emerged as a promising strategy to address these challenges. In this study, we developed a biodegradable nanosystem, designated CSZG, which integrates glucose oxidase (GOx) and copper-rich copper selenide (Cu\n                    <jats:sub>\n                      2\u2212\n                      <jats:italic toggle=\"yes\">x<\/jats:italic>\n                    <\/jats:sub>\n                    Se) within a ZIF-8 nanocarrier for lung cancer therapy. CSZG exhibited pH-responsive GOx release, favorable colloidal stability, and retained glucose-responsive catalytic activity of GOx. GOx supplied hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) through glucose oxidation, while Cu\n                    <jats:sup>+<\/jats:sup>\n                    catalyzed the conversion of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    into cytotoxic hydroxyl radicals (\u2022OH) under near-infrared (NIR) irradiation, thereby enhancing chemodynamic therapy. Electron spin resonance analysis directly confirmed NIR-enhanced \u2022OH generation, particularly under acidic conditions. In addition, CSZG + NIR induced copper-dependent mitochondrial dysfunction with cuproptosis-associated features, as evidenced by aggregation of dihydrolipoamide S-acetyltransferase, down-regulation of ferredoxin 1 , depletion of Fe\u2013S cluster proteins, and partial reversal by tetrathiomolybdate. The Cu\n                    <jats:sub>\n                      2\u2212\n                      <jats:italic toggle=\"yes\">x<\/jats:italic>\n                    <\/jats:sub>\n                    Se-containing platform also promoted macrophage polarization toward an M1-like phenotype. In\u00a0vivo, CSZG + NIR achieved a tumor inhibition rate of 91.7% and demonstrated favorable short-term systemic biosafety under the tested therapeutic conditions. Collectively, these findings highlight CSZG as a promising multimodal therapeutic platform for lung cancer.\n                  <\/jats:p>","DOI":"10.34133\/bmr.0404","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:50:52Z","timestamp":1785455452000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["A Degradable Nanoplatform Integrating Glucose Oxidase and Copper Selenide for Near-Infrared-Enhanced Multimodal Synergistic Therapy in Lung Cancer"],"prefix":"10.34133","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1631-7048","authenticated-orcid":true,"given":"Yong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pulmonary, Zhongshan Hospital, \rFudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, \rThe Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary, Zhongshan Hospital, \rFudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengni","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, \rEast China Normal University, Shanghai 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, \rThe Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Degang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, \rThe Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, \rThe Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiebai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pulmonary, Zhongshan Hospital, \rFudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary, Zhongshan Hospital, \rFudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary, Zhongshan Hospital, \rFudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangzhou","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, \rThe Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, 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