A glutathione-responsive ferroptotic inducer with elevated labile iron pool and self-supplied peroxide for chemodynamic therapy
Chemodynamic therapy (CDT) is a novel approach in the treatment of tumors in which ferrous iron (Fe2+) is the primary catalyst of the Fenton reaction. However, Fe2+ is typically stored in an oxidized mineral form as ferric iron (Fe3+) in ferritin, significantly limiting the efficacy of CDT. This wor...
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Elsevier
2025-06-01
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| author | Penghui Wei Xuegang Niu Dengliang Wang Chengzhong Du Mingtao Zhu Hongjia Zheng Yongrui Hu Yu Tian Wei Huang Chengyu Ding Yuanxiang Lin Yang Zhu Dezhi Kang |
| author_facet | Penghui Wei Xuegang Niu Dengliang Wang Chengzhong Du Mingtao Zhu Hongjia Zheng Yongrui Hu Yu Tian Wei Huang Chengyu Ding Yuanxiang Lin Yang Zhu Dezhi Kang |
| author_sort | Penghui Wei |
| collection | DOAJ |
| description | Chemodynamic therapy (CDT) is a novel approach in the treatment of tumors in which ferrous iron (Fe2+) is the primary catalyst of the Fenton reaction. However, Fe2+ is typically stored in an oxidized mineral form as ferric iron (Fe3+) in ferritin, significantly limiting the efficacy of CDT. This work describes the preparation of redox-responsive nanoparticles (MO@DSSP NPs) embedded with OSMI-1 and methyl linoleate hydroperoxide (MLH) to synergistically enhance CDT efficacy, optimize peroxide supply and deplete glutathione (GSH). The redox-responsive MO@DSSP NPs undergo disintegration after being internalized by tumor cells due to the reductive tumor microenvironment, consuming GSH while releasing OSMI-1 and MLH. This process increases the intracellular labile iron pool (LIP) and oxidative stress at the tumor site by inhibiting O-GlcNAcylation of ferritin heavy chain (FTH). Furthermore, obstructing O-GlcNAc modification triggers mitochondrial fragmentation alongside autophagy, thus contributing an extra source of reactive iron. The increased LIP significantly promotes the generation of hydroxyl radical (·OH) that causes lipid peroxidation, consequent damage of the cell membrane and ferroptosis. Therefore, this study describes an attractive CDT nanoagent that effectively inhibits the O-GlcNAcylation of FTH to mobilize endogenous Fenton-type metals, as well as offers a basis to the exploration of LIP-activatable MLH with high CDT efficacy, demonstrating significant potential for clinical applications. |
| format | Article |
| id | doaj-art-2b91c0251fd146d9b1eb66e328f54e70 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-2b91c0251fd146d9b1eb66e328f54e702025-08-20T03:26:35ZengElsevierMaterials Today Bio2590-00642025-06-013210191310.1016/j.mtbio.2025.101913A glutathione-responsive ferroptotic inducer with elevated labile iron pool and self-supplied peroxide for chemodynamic therapyPenghui Wei0Xuegang Niu1Dengliang Wang2Chengzhong Du3Mingtao Zhu4Hongjia Zheng5Yongrui Hu6Yu Tian7Wei Huang8Chengyu Ding9Yuanxiang Lin10Yang Zhu11Dezhi Kang12Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Corresponding author. Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China.Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, Xiamen Xinglin Hospital (Xiamen Infectious Disease Hospital), Xiamen, 361000, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Corresponding author. Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China.Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Provincial Institutes of Brain Disorders and Brain Sciences, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China; Corresponding author. Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 35005, China.Chemodynamic therapy (CDT) is a novel approach in the treatment of tumors in which ferrous iron (Fe2+) is the primary catalyst of the Fenton reaction. However, Fe2+ is typically stored in an oxidized mineral form as ferric iron (Fe3+) in ferritin, significantly limiting the efficacy of CDT. This work describes the preparation of redox-responsive nanoparticles (MO@DSSP NPs) embedded with OSMI-1 and methyl linoleate hydroperoxide (MLH) to synergistically enhance CDT efficacy, optimize peroxide supply and deplete glutathione (GSH). The redox-responsive MO@DSSP NPs undergo disintegration after being internalized by tumor cells due to the reductive tumor microenvironment, consuming GSH while releasing OSMI-1 and MLH. This process increases the intracellular labile iron pool (LIP) and oxidative stress at the tumor site by inhibiting O-GlcNAcylation of ferritin heavy chain (FTH). Furthermore, obstructing O-GlcNAc modification triggers mitochondrial fragmentation alongside autophagy, thus contributing an extra source of reactive iron. The increased LIP significantly promotes the generation of hydroxyl radical (·OH) that causes lipid peroxidation, consequent damage of the cell membrane and ferroptosis. Therefore, this study describes an attractive CDT nanoagent that effectively inhibits the O-GlcNAcylation of FTH to mobilize endogenous Fenton-type metals, as well as offers a basis to the exploration of LIP-activatable MLH with high CDT efficacy, demonstrating significant potential for clinical applications.http://www.sciencedirect.com/science/article/pii/S2590006425004831Chemodynamic therapyFerritin heavy chainLabile iron poolO-GlcNAcylationFerroptosis |
| spellingShingle | Penghui Wei Xuegang Niu Dengliang Wang Chengzhong Du Mingtao Zhu Hongjia Zheng Yongrui Hu Yu Tian Wei Huang Chengyu Ding Yuanxiang Lin Yang Zhu Dezhi Kang A glutathione-responsive ferroptotic inducer with elevated labile iron pool and self-supplied peroxide for chemodynamic therapy Materials Today Bio Chemodynamic therapy Ferritin heavy chain Labile iron pool O-GlcNAcylation Ferroptosis |
| title | A glutathione-responsive ferroptotic inducer with elevated labile iron pool and self-supplied peroxide for chemodynamic therapy |
| title_full | A glutathione-responsive ferroptotic inducer with elevated labile iron pool and self-supplied peroxide for chemodynamic therapy |
| title_fullStr | A glutathione-responsive ferroptotic inducer with elevated labile iron pool and self-supplied peroxide for chemodynamic therapy |
| title_full_unstemmed | A glutathione-responsive ferroptotic inducer with elevated labile iron pool and self-supplied peroxide for chemodynamic therapy |
| title_short | A glutathione-responsive ferroptotic inducer with elevated labile iron pool and self-supplied peroxide for chemodynamic therapy |
| title_sort | glutathione responsive ferroptotic inducer with elevated labile iron pool and self supplied peroxide for chemodynamic therapy |
| topic | Chemodynamic therapy Ferritin heavy chain Labile iron pool O-GlcNAcylation Ferroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425004831 |
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