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This study reports the development of a biomimetic nanosystem, termed R\u2010CM@MSN@BC, integrating mesoporous organosilicon nanoparticles with reactive oxygen species\u2010responsive diselenide bonds for controlled release of the glutamine metabolism inhibitor bis\u20102\u2010(5\u2010phenylacetamido\u20101,3,4\u2010thiadiazol\u20102\u2010yl) ethyl sulfide (BPTES) and the photosensitizer Ce6. Erythrocyte membrane coating, engineered with Arg\u2010Gly\u2010Asp (RGD) peptides, not only enhanced biocompatibility but also improved tumor targeting and tissue penetration. Upon laser irradiation, R\u2010CM@MSN@BC executed both photodynamic and glutamine\u2010metabolic therapies, inducing necroptosis in tumor cells and triggering significant immunogenic cell death. Time\u2010of\u2010flight mass cytometry analysis revealed that R\u2010CM@MSN@BC can remodel the immunosuppressive tumor microenvironment by polarizing M1\u2010type macrophages, reducing infiltration of M2\u2010type and CX3CR1<jats:sup>+<\/jats:sup> macrophages, and decreasing T cell exhaustion, thereby increasing the effectiveness of anti\u2010programmed cell death ligand 1 immunotherapy. This strategy proposed in this study presents a viable and promising approach for the treatment of cholangiocarcinoma.<\/jats:p>","DOI":"10.1002\/advs.202309203","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T07:19:56Z","timestamp":1717571996000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Necroptosis\u2010Mediated Synergistic Photodynamic and Glutamine\u2010Metabolic Therapy Enabled by a Biomimetic Targeting Nanosystem for Cholangiocarcinoma"],"prefix":"10.1002","volume":"11","author":[{"given":"Qichang","family":"Zheng","sequence":"first","affiliation":[{"name":"Center for Liver Transplantation Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhao","family":"Zou","sequence":"additional","affiliation":[{"name":"Center for Liver Transplantation Union 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