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However, the efficacy of PDT is hindered by intratumoral hypoxia and the presence of an antioxidant microenvironment. To address these limitations, combining PDT with gas therapy may be a promising strategy to enhance tumor oxygenation. Moreover, the augmentation of oxidative damage induced by PDT and gas therapy can be achieved by inhibiting NRF2, a core regulatory molecule involved in the antioxidant response. In this study, an integrated nanotherapeutic platform called CMArg@Lip, incorporating PDT and gas therapies using ROS\u2010responsive liposomes encapsulating the photosensitizer Ce6, the NO gas\u2010generating agent L\u2010arginine, and the NRF2 inhibitor ML385, is successfully developed. The utilization of CMArg@Lip effectively deals with challenges posed by tumor hypoxia and antioxidant microenvironment, resulting in elevated levels of oxidative damage and subsequent induction of ferroptosis in CCA. Additionally, these findings suggest that CMArg@Lip exhibits notable immunomodulatory effects, including the promotion of immunogenic cell death and facilitation of dendritic cell maturation. Furthermore, it contributes to the anti\u2010tumor function of cytotoxic T lymphocytes through the downregulation of PD\u2010L1 expression in tumor cells and the activation of the STING signaling pathway in myeloid\u2010derived suppressor cells, thereby reprogramming the immunosuppressive microenvironment via various mechanisms.<\/jats:p>","DOI":"10.1002\/advs.202307143","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T23:00:57Z","timestamp":1706914857000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A NRF2 Regulated and the Immunosuppressive Microenvironment Reversed Nanoplatform for Cholangiocarcinoma Photodynamic\u2010Gas Therapy"],"prefix":"10.1002","volume":"11","author":[{"given":"Weimin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology 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