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However, formidable challenges, such as innate and adaptive immune resistance, along with the off\u2010target adverse effects of nonselective immunomodulators, persist. In this study, a tumor\u2010selective nano\u2010regulator named PNBJQ has been presented, focusing on targeting two nonredundant immune nodes: inducing immunogenic cancer cell death and abrogating immune resistance to fully activate endogenous tumor immunity. PNBJQ is obtained by encapsulating the immunomodulating agent JQ1 within a self\u2010assembling system formed by linking a Type\u2010I photosensitizer to polyethylene glycol through a hypoxia\u2010sensitive azo bond. Benefiting from the Type\u2010I photosensitive mechanism, PNBJQ triggers the immunogenic cell death of hypoxic tumors under near\u2010infrared (NIR)\u00a0light irradiation. This process resolves innate immune resistance by stimulating sufficient cytotoxic T\u2010lymphocytes. Simultaneously, PNBJQ smartly responds to the hypoxic tumor microenvironment for precise drug delivery, adeptly addressing adaptive immune resistance by using JQ1 to downregulate programmed death ligand 1 (PD\u2010L1) and sustaining the response of cytotoxic T lymphocytes. The activatable synergic photoimmunotherapy promotes an immune\u2010promoting tumor microenvironment by activating an iterative revolution of the CIC, which remarkably eradicates established hypoxic tumors and suppresses distal lesions under low light dose irradiation.<\/jats:p>","DOI":"10.1002\/adma.202400196","type":"journal-article","created":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T00:29:55Z","timestamp":1715473795000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Activating Iterative Revolutions of the Cancer\u2010Immunity Cycle in Hypoxic Tumors with a Smart Nano\u2010Regulator"],"prefix":"10.1002","volume":"36","author":[{"given":"Junying","family":"Ding","sequence":"first","affiliation":[{"name":"State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Dalian University of Technology  Dalian 116024 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