Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapy
The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NPFeS/GD) had been developed to effectively augment antitu...
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| Format: | Article |
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Elsevier
2025-03-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383524004714 |
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| author | Yingli Luo Maoyuan Linghu Xianyu Luo Dongdong Li Jilong Wang Shaojun Peng Yinchu Ma |
| author_facet | Yingli Luo Maoyuan Linghu Xianyu Luo Dongdong Li Jilong Wang Shaojun Peng Yinchu Ma |
| author_sort | Yingli Luo |
| collection | DOAJ |
| description | The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NPFeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H2S amplification. The bioactive NPFeS/GD exhibited controlled release of GSDMD plasmid, H2S, and Fe2+ in response to the tumor microenvironment. Fe2+, H2S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H2S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NPFeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H2S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment. |
| format | Article |
| id | doaj-art-2d50e4d05f9e43acb2d11d3cafcbee5d |
| institution | OA Journals |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-2d50e4d05f9e43acb2d11d3cafcbee5d2025-08-20T01:53:23ZengElsevierActa Pharmaceutica Sinica B2211-38352025-03-011531242125410.1016/j.apsb.2024.12.014Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapyYingli Luo0Maoyuan Linghu1Xianyu Luo2Dongdong Li3Jilong Wang4Shaojun Peng5Yinchu Ma6Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China; Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi 214062, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaJoint Centre of Translational Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, ChinaJoint Centre of Translational Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, ChinaCenter for Biological Science and Technology & College of Arts and Sciences, Beijing Normal University, Zhuhai 519087, China; Corresponding authors.Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China; Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi 214062, China; Corresponding authors.The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NPFeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H2S amplification. The bioactive NPFeS/GD exhibited controlled release of GSDMD plasmid, H2S, and Fe2+ in response to the tumor microenvironment. Fe2+, H2S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H2S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NPFeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H2S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment.http://www.sciencedirect.com/science/article/pii/S2211383524004714PANoptosisFerroptosisNanomedicineH2S gas therapyImmunogenic cell deathRemodeling immunosuppressive microenvironment |
| spellingShingle | Yingli Luo Maoyuan Linghu Xianyu Luo Dongdong Li Jilong Wang Shaojun Peng Yinchu Ma Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapy Acta Pharmaceutica Sinica B PANoptosis Ferroptosis Nanomedicine H2S gas therapy Immunogenic cell death Remodeling immunosuppressive microenvironment |
| title | Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapy |
| title_full | Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapy |
| title_fullStr | Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapy |
| title_full_unstemmed | Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapy |
| title_short | Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapy |
| title_sort | remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by h2s amplified nanoformulation to enhance cancer immunotherapy |
| topic | PANoptosis Ferroptosis Nanomedicine H2S gas therapy Immunogenic cell death Remodeling immunosuppressive microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2211383524004714 |
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