Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis
As a non-apoptotic cell death form, ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance. However, accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms. To address this issue, we prepared a Buthi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Asian Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1818087622001192 |
| _version_ | 1797894930085969920 |
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| author | Chengcheng Wang Jiao Wang Xue Pan Shuang Yu Meiqi Chen Yan Gao Zilin Song Haiyang Hu Xiuli Zhao Dawei Chen Fei Han Mingxi Qiao |
| author_facet | Chengcheng Wang Jiao Wang Xue Pan Shuang Yu Meiqi Chen Yan Gao Zilin Song Haiyang Hu Xiuli Zhao Dawei Chen Fei Han Mingxi Qiao |
| author_sort | Chengcheng Wang |
| collection | DOAJ |
| description | As a non-apoptotic cell death form, ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance. However, accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms. To address this issue, we prepared a Buthionine-(S,R)-sulfoximine (BSO) loaded metal organic framework (MOF) of BSO-MOF-HA (BMH) with the combination effect of boosting oxidative damage and inhibiting antioxidative defense. MOF nanoparticle was constructed by the photosensitizer of [4,4,4,4-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid)] (TCPP) and the metal ion of Zr6, which was further decorated with hyaluronic acid (HA) in order to impart active targeting to CD44 receptors overexpressed cancer cells. BMH exhibited a negative charge and spherical shape with average particle size about 162.5 nm. BMH was found to restore the susceptibility of 4T1 cells to ferroptosis under irradiation. This was attributed to the combination of photodynamic therapy (PDT) and γ-glutamylcysteine synthetase inhibitor of BSO, shifting the redox balance to oxidative stress. Enhanced ferroptosis also induced the release of damage associated molecular patterns (DAMPs) to maturate dendritic cells and activated T lymphocytes, leading to superior anti-tumor performance in vivo. Taken together, our findings demonstrated that boosting oxidative damage with photosensitizer serves as an effective strategy to reverse ferroptosis resistance. |
| first_indexed | 2024-04-10T07:17:09Z |
| format | Article |
| id | doaj.art-4206b228ed6e4816bad54e8b719510be |
| institution | Directory Open Access Journal |
| issn | 1818-0876 |
| language | English |
| last_indexed | 2024-04-10T07:17:09Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-4206b228ed6e4816bad54e8b719510be2023-02-25T04:09:33ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762023-01-01181100770Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasisChengcheng Wang0Jiao Wang1Xue Pan2Shuang Yu3Meiqi Chen4Yan Gao5Zilin Song6Haiyang Hu7Xiuli Zhao8Dawei Chen9Fei Han10Mingxi Qiao11School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaYantai Luyin Pharmaceutical Co. Ltd., Yantai 264002, ChinaQingdao Marine Biomedical Research Institute, Qingdao 266071, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; Corresponding authors.School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; Corresponding authors.As a non-apoptotic cell death form, ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance. However, accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms. To address this issue, we prepared a Buthionine-(S,R)-sulfoximine (BSO) loaded metal organic framework (MOF) of BSO-MOF-HA (BMH) with the combination effect of boosting oxidative damage and inhibiting antioxidative defense. MOF nanoparticle was constructed by the photosensitizer of [4,4,4,4-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid)] (TCPP) and the metal ion of Zr6, which was further decorated with hyaluronic acid (HA) in order to impart active targeting to CD44 receptors overexpressed cancer cells. BMH exhibited a negative charge and spherical shape with average particle size about 162.5 nm. BMH was found to restore the susceptibility of 4T1 cells to ferroptosis under irradiation. This was attributed to the combination of photodynamic therapy (PDT) and γ-glutamylcysteine synthetase inhibitor of BSO, shifting the redox balance to oxidative stress. Enhanced ferroptosis also induced the release of damage associated molecular patterns (DAMPs) to maturate dendritic cells and activated T lymphocytes, leading to superior anti-tumor performance in vivo. Taken together, our findings demonstrated that boosting oxidative damage with photosensitizer serves as an effective strategy to reverse ferroptosis resistance.http://www.sciencedirect.com/science/article/pii/S1818087622001192FerroptosisButhionine-(S,R)-sulfoximineGlutathioneMetal organic frameworkPhotodynamic therapyImmunogenic cell death |
| spellingShingle | Chengcheng Wang Jiao Wang Xue Pan Shuang Yu Meiqi Chen Yan Gao Zilin Song Haiyang Hu Xiuli Zhao Dawei Chen Fei Han Mingxi Qiao Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis Asian Journal of Pharmaceutical Sciences Ferroptosis Buthionine-(S,R)-sulfoximine Glutathione Metal organic framework Photodynamic therapy Immunogenic cell death |
| title | Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis |
| title_full | Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis |
| title_fullStr | Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis |
| title_full_unstemmed | Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis |
| title_short | Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis |
| title_sort | reversing ferroptosis resistance by mofs through regulation intracellular redox homeostasis |
| topic | Ferroptosis Buthionine-(S,R)-sulfoximine Glutathione Metal organic framework Photodynamic therapy Immunogenic cell death |
| url | http://www.sciencedirect.com/science/article/pii/S1818087622001192 |
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