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Here, this work designs hybrid drug\u2010loaded nanoliposomes by co\u2010loading the chemotherapeutic drug temozolomide (TMZ) and nitric oxide (NO) prodrug JS\u2010K with sphingosine\u20101\u2010phosphate molecules (S1P) on the surface. The S1P\u2010S1P receptors axis endows nanoliposomes with rapid targeting and lysosomal escaping capability. Then, fine\u2010tuned TMZ release and NO gas production following JS\u2010K release in glioma microenvironment decrease chemoresistance and increase tumor immunogenicity through inhibiting the cellular autophagy as well as inducing mitochondrial dysfunction. RNA sequencing analysis demonstrates that the NO gas generation reprograms glioma microenvironment immune and inflammation\u2010related pathways. The positive immune response in turn effectively activates the enhanced efficacy of chemotherapy. NO gas generated nanoliposomes thus have attractive paradigm\u2010shifting applications in the treatment of \u201ccold\u201d tumors across a range of immunosuppressive indications.<\/jats:p>","DOI":"10.1002\/advs.202300679","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T23:11:39Z","timestamp":1682118699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["In Situ Nitric Oxide Gas Nanogenerator Reprograms Glioma Immunosuppressive Microenvironment"],"prefix":"10.1002","volume":"10","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Sciences and Medical Engineering Southeast University  Nanjing 210096 P. R. 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