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Here, we develop an oxygen\u2011amplified carrier\u2011free nanomedicine (IHC NPs) through hydrophobic self\u2011assembly of IR-820, hemin, and celecoxib. IHC NPs exhibit excellent stability, biological safety, and preferential tumor accumulation. In the subcutaneous glioma model, the combination of IHC NPs and \u03b1PD-L1 significantly inhibited subcutaneous tumor growth and effectively prevented distant tumor metastasis. Mechanistically, hemin catalyzes endogenous H2O2 to generate oxygen, thereby alleviating tumor hypoxia. This oxygen boost potentiates IR-820\u2011mediated photodynamic therapy and hemin-based ferroptosis, enhancing direct tumor cell killing. Concurrently, celecoxib blocks the COX\u20112\/PGE2 pathway, reversing immunosuppression within the tumor microenvironment. Through the synergistic strategy combining oxygen-sensitized photodynamic therapy, ferroptosis, COX-2\/PGE2 suppression, and PD-1\/PD-L1 blockade, this therapeutic regimen effectively induces tumor immunogenic cell death, promotes dendritic cell maturation, enhances intratumoral infiltration of cytotoxic T lymphocytes, reduces the abundance of regulatory T cells, and triggers the generation of effector memory T cells, thereby potently activating the host immune system. Collectively, our work provides a promising oxygen\u2011amplified carrier\u2011free nanomedicine for robust glioma immunotherapy.<\/jats:p>","DOI":"10.1021\/acsami.6c14380","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:07:06Z","timestamp":1792008426000},"page":"57145-57160","source":"Crossref","is-referenced-by-count":0,"title":["Oxygen-Amplified Carrier-Free Nanomedicine Integrating Ferroptosis\/Photodynamic Therapy and COX-2\/PGE2 Blockade for Robust Antitumor Immunity Against Glioma"],"prefix":"10.1021","volume":"18","author":[{"given":"Yinxing","family":"Huang","sequence":"first","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University , , ,","place":["Fuzhou, China, 350025"]},{"name":"Fujian Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Neurovascular Diseases of Fujian Medical University , ,","place":["Fuzhou, China, 350025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University , , ,","place":["Fuzhou, China, 350025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhong","family":"Pan","sequence":"additional","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University , , ,","place":["Fuzhou, China, 350025"]},{"name":"Fujian Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Neurovascular Diseases of Fujian Medical University , ,","place":["Fuzhou, China, 350025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaikai","family":"Huang","sequence":"additional","affiliation":[{"name":"Fuzong Teaching Hospital of Fujian University of Traditional Chinese Medicine (900th Hospital) , , ,","place":["Fuzhou, China, 350025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Wu","sequence":"additional","affiliation":[{"name":"Huaqiao University , , ,","place":["Quanzhou, China, 362021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2183-9635","authenticated-orcid":true,"given":"Xianquan","family":"Feng","sequence":"additional","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University , , ,","place":["Fuzhou, China, 350025"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"issue":"7","key":"2026102801071038300_cit1","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1001\/jama.2023.0023","article-title":"Glioblastoma and Other Primary Brain Malignancies in Adults: A Review","volume":"329","author":"Schaff","year":"2023","journal-title":"JAMA"},{"issue":"12 Suppl 2","key":"2026102801071038300_cit2","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/noad149","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016\u20132020","volume":"25","author":"Ostrom","year":"2016","journal-title":"Neuro Oncol."},{"issue":"2","key":"2026102801071038300_cit3","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1093\/neuonc\/noaf236","article-title":"T cell immunity in glioma and potential implications for immunotherapy: A systematic review","volume":"28","author":"Luning","year":"2026","journal-title":"Neuro Oncol."},{"issue":"12","key":"2026102801071038300_cit4","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009175","article-title":"Co-evolution of glioma and immune microenvironment","volume":"12","author":"Elguindy","year":"2024","journal-title":"J. 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