Radiation-induced ferroptosis via liposomal delivery of 7-Dehydrocholesterol
Abstract Background Ferroptosis is an emerging cell death mechanism characterized by uncontrolled lipid peroxidation. However, selectively inducing ferroptosis in cancer cells remains a challenge. Methods We explore an approach that enables ferroptosis induction through external radiation. The key c...
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BMC
2025-03-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03303-3 |
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| author | Jianwen Li Shuyue Zhan Wei Yang He Zhang Xinrui Ma Fanghui Chen Amy Li Pakteema Tong Fangchao Jiang Zhengwei Cao Ian Delahunty Jiayi Wang Yufei Wu Zhi Liu Zibo Li Yong Teng Libin Xu Jin Xie |
| author_facet | Jianwen Li Shuyue Zhan Wei Yang He Zhang Xinrui Ma Fanghui Chen Amy Li Pakteema Tong Fangchao Jiang Zhengwei Cao Ian Delahunty Jiayi Wang Yufei Wu Zhi Liu Zibo Li Yong Teng Libin Xu Jin Xie |
| author_sort | Jianwen Li |
| collection | DOAJ |
| description | Abstract Background Ferroptosis is an emerging cell death mechanism characterized by uncontrolled lipid peroxidation. However, selectively inducing ferroptosis in cancer cells remains a challenge. Methods We explore an approach that enables ferroptosis induction through external radiation. The key component of this technology is 7-dehydrocholesterol (7DHC), a natural biosynthetic precursor of cholesterol. To facilitate delivery, we demonstrate that 7DHC, like cholesterol, can be incorporated into the lipid layer of liposomes. To enhance targeting, we also introduced NTSmut, a ligand for the neurotensin receptor 1 (NTSR1), which is overexpressed in multiple malignancies, into liposomes. Results Under radiation, 7DHC reacts with radiation-induced reactive oxygen species (ROS), initiating a radical chain reaction with polyunsaturated fatty acids (PUFAs) in cell membranes. This process results in direct lipid peroxidation and subsequent ferroptotic cell death. In vivo studies demonstrate that NTSmut-conjugated, 7DHC-loaded liposomes (N-7DHC-lipos) effectively accumulate in tumors and significantly enhance the efficacy of radiation therapy. Conclusion While conventional radiosensitizers primarily target DNA and its repair mechanisms, our study introduces a strategy to enhance radiotherapy by specifically activating ferroptosis within the irradiated area, thereby minimizing systemic toxicity. Such a strategy of controlled activation of ferroptosis offers a favorable therapeutic index and potentially opens avenues for clinical application. |
| format | Article |
| id | doaj-art-ae7d3b02af2a44b7bdb74e277f5928a6 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-ae7d3b02af2a44b7bdb74e277f5928a62025-08-20T03:40:47ZengBMCJournal of Nanobiotechnology1477-31552025-03-0123111710.1186/s12951-025-03303-3Radiation-induced ferroptosis via liposomal delivery of 7-DehydrocholesterolJianwen Li0Shuyue Zhan1Wei Yang2He Zhang3Xinrui Ma4Fanghui Chen5Amy Li6Pakteema Tong7Fangchao Jiang8Zhengwei Cao9Ian Delahunty10Jiayi Wang11Yufei Wu12Zhi Liu13Zibo Li14Yong Teng15Libin Xu16Jin Xie17Department of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Radiology, University of North Carolina at Chapel HillDepartment of Radiology, University of North Carolina at Chapel HillDepartment of Hematology and Medical Oncology & Winship Cancer Institute, Emory University School of MedicineDepartment of Medicinal Chemistry, University of WashingtonDepartment of Medicinal Chemistry, University of WashingtonDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Radiology, University of North Carolina at Chapel HillDepartment of Hematology and Medical Oncology & Winship Cancer Institute, Emory University School of MedicineDepartment of Medicinal Chemistry, University of WashingtonDepartment of Chemistry, University of GeorgiaAbstract Background Ferroptosis is an emerging cell death mechanism characterized by uncontrolled lipid peroxidation. However, selectively inducing ferroptosis in cancer cells remains a challenge. Methods We explore an approach that enables ferroptosis induction through external radiation. The key component of this technology is 7-dehydrocholesterol (7DHC), a natural biosynthetic precursor of cholesterol. To facilitate delivery, we demonstrate that 7DHC, like cholesterol, can be incorporated into the lipid layer of liposomes. To enhance targeting, we also introduced NTSmut, a ligand for the neurotensin receptor 1 (NTSR1), which is overexpressed in multiple malignancies, into liposomes. Results Under radiation, 7DHC reacts with radiation-induced reactive oxygen species (ROS), initiating a radical chain reaction with polyunsaturated fatty acids (PUFAs) in cell membranes. This process results in direct lipid peroxidation and subsequent ferroptotic cell death. In vivo studies demonstrate that NTSmut-conjugated, 7DHC-loaded liposomes (N-7DHC-lipos) effectively accumulate in tumors and significantly enhance the efficacy of radiation therapy. Conclusion While conventional radiosensitizers primarily target DNA and its repair mechanisms, our study introduces a strategy to enhance radiotherapy by specifically activating ferroptosis within the irradiated area, thereby minimizing systemic toxicity. Such a strategy of controlled activation of ferroptosis offers a favorable therapeutic index and potentially opens avenues for clinical application.https://doi.org/10.1186/s12951-025-03303-3Liposomes7-dehydrocholesterolRadiosensitizerLipid peroxidationFerroptosis |
| spellingShingle | Jianwen Li Shuyue Zhan Wei Yang He Zhang Xinrui Ma Fanghui Chen Amy Li Pakteema Tong Fangchao Jiang Zhengwei Cao Ian Delahunty Jiayi Wang Yufei Wu Zhi Liu Zibo Li Yong Teng Libin Xu Jin Xie Radiation-induced ferroptosis via liposomal delivery of 7-Dehydrocholesterol Journal of Nanobiotechnology Liposomes 7-dehydrocholesterol Radiosensitizer Lipid peroxidation Ferroptosis |
| title | Radiation-induced ferroptosis via liposomal delivery of 7-Dehydrocholesterol |
| title_full | Radiation-induced ferroptosis via liposomal delivery of 7-Dehydrocholesterol |
| title_fullStr | Radiation-induced ferroptosis via liposomal delivery of 7-Dehydrocholesterol |
| title_full_unstemmed | Radiation-induced ferroptosis via liposomal delivery of 7-Dehydrocholesterol |
| title_short | Radiation-induced ferroptosis via liposomal delivery of 7-Dehydrocholesterol |
| title_sort | radiation induced ferroptosis via liposomal delivery of 7 dehydrocholesterol |
| topic | Liposomes 7-dehydrocholesterol Radiosensitizer Lipid peroxidation Ferroptosis |
| url | https://doi.org/10.1186/s12951-025-03303-3 |
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