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The COX\u20102\/PGE2 signaling axis has been identified as a crucial regulator in the establishment of immunosuppressive conditions. Herein, this work developed an excipient\u2010free nanomedicine (IPC NPs) via non\u2010covalent self\u2010assembly, integrating indocyanine green and paclitaxel (dual ICD inducers) with celecoxib (COX\u20102\/PGE2 inhibitor) for combined chemo\u2010photothermal therapy with anti\u2010inflammatory effects. The IPC NPs displayed monodisperse characteristics with optimal near\u2010infrared responsiveness, significantly enhancing tumor tissue permeation while demonstrating synergistic chemo\u2010photothermal cytotoxicity against triple\u2010negative breast cancer (TNBC). Notably, IPC NPs\u2010encapsulated celecoxib effectively remodeled the tumor inflammatory microenvironment by attenuating therapy\u2010induced inflammatory responses, thereby potentiating ICD. This triple therapy regimen promoted dendritic cell maturation, enhanced cytotoxic T lymphocyte infiltration into tumor tissues, and upregulated effector memory T cell populations in TNBC. These immunomodulatory effects substantially ameliorated the immunosuppressive tumor microenvironment, leading to significant inhibition of primary tumor growth and metastasis. Collectively, this work presents a novel carrier\u2010free nanotherapeutic strategy that synergistically combines chemo\u2010photothermal\u2010inflammatory suppression therapy, offering a promising approach for TNBC.<\/jats:p>","DOI":"10.1002\/smll.202512540","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T14:35:08Z","timestamp":1770734108000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Self\u2010Assembled Carrier\u2010Free Nanomedicines Potentiate Chemo\u2010Photothermal Immunotherapy by Overcoming Prostaglandin E2\u2010Mediated Immunosuppression"],"prefix":"10.1002","volume":"22","author":[{"given":"Xiaoliang","family":"Deng","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory of Transplant Biology of Laboratory of Basic Medicine Fuzong Teaching Hospital of Fujian University of Traditional Chinese Medicine (900th Hospital)  Fuzhou 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