biostudies-literatureLiu YFundamental Research Funds for the Central UniversitiesJiangsu Excellent Postdoctoral ProgramChina Postdoctoral Science FoundationNational Natural Science Foundation of ChinaNational Key Research and Development Program of Chinae2300679https://www.ebi.ac.uk/biostudies/studies/S-EPMC10288280biostudies-literatureUnknown10(18)Universal chemotherapy in glioblastoma patients causes chemoresistance and further limits immune cells by creating an immunosuppressive tumor microenvironment that are difficult to solve by single-drug therapeutic approaches. Here, this work designs hybrid drug-loaded nanoliposomes by co-loading the chemotherapeutic drug temozolomide (TMZ) and nitric oxide (NO) prodrug JS-K with sphingosine-1-phosphate molecules (S1P) on the surface. The S1P-S1P receptors axis endows nanoliposomes with rapid targeting and lysosomal escaping capability. Then, fine-tuned TMZ release and NO gas production following JS-K release in glioma microenvironment decrease chemoresistance and increase tumor immunogenicity through inhibiting the cellular autophagy as well as inducing mitochondrial dysfunction. RNA sequeAdvanced science (Weinheim, Baden-Wurttemberg, Germany)In Situ Nitric Oxide Gas Nanogenerator Reprograms Glioma Immunosuppressive Microenvironment.PMC102882802242022R200432022M7106872022T150117819717502018YFA07041032022ZB124Liu YCui LJu YWang XMiao WXu HGu NYang FChen TfalseIn Situ Nitric Oxide Gas Nanogenerator Reprograms Glioma Immunosuppressive Microenvironment.Universal chemotherapy in glioblastoma patients causes chemoresistance and further limits immune cells by creating an immunosuppressive tumor microenvironment that are difficult to solve by single-drug therapeutic approaches. Here, this work designs hybrid drug-loaded nanoliposomes by co-loading the chemotherapeutic drug temozolomide (TMZ) and nitric oxide (NO) prodrug JS-K with sphingosine-1-phosphate molecules (S1P) on the surface. The S1P-S1P receptors axis endows nanoliposomes with rapid targeting and lysosomal escaping capability. Then, fine-tuned TMZ release and NO gas production following JS-K release in glioma microenvironment decrease chemoresistance and increase tumor immunogenicity through inhibiting the cellular autophagy as well as inducing mitochondrial dysfunction. RNA seque2023-01-01T00:00:00Z2023 Jun2025-04-05T12:14:16.88Z2025-02-19T04:29:17.277ZS-EPMC102882803708566310.1002/advs.202300679