A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapy
Abstract Osteosarcoma treatment remains challenging due to the limitations of single-modality therapies. To address this, we designed a carrier-free nanomedicine SRF@CuSO4.5H2O@IR780 (CSIR) for synergistic ferroptosis, photodynamic therapy (PDT), and photothermal therapy (PTT) in osteosarcoma. Inter...
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| Format: | Article |
| Language: | English |
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BMC
2025-04-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03380-4 |
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| author | Tangbing Xu Qiming Ma Chi Zhang Xiaoyan He Qian Wang Yunfeng Wu Kunpeng Qin Faxue Liao Ping Zhou Pengfei Xu Jialai Yang Junjun Yang Jun Chang Lei Qiao Yong Hu |
| author_facet | Tangbing Xu Qiming Ma Chi Zhang Xiaoyan He Qian Wang Yunfeng Wu Kunpeng Qin Faxue Liao Ping Zhou Pengfei Xu Jialai Yang Junjun Yang Jun Chang Lei Qiao Yong Hu |
| author_sort | Tangbing Xu |
| collection | DOAJ |
| description | Abstract Osteosarcoma treatment remains challenging due to the limitations of single-modality therapies. To address this, we designed a carrier-free nanomedicine SRF@CuSO4.5H2O@IR780 (CSIR) for synergistic ferroptosis, photodynamic therapy (PDT), and photothermal therapy (PTT) in osteosarcoma. Interestingly, CSIR could harness the enhanced permeability and retention (EPR) effect to effectively enter tumors. Copper ions (Cu2+) within CSIR could react with the reductive intracellular environment, depleting glutathione (GSH) levels. Near-infrared (NIR) irradiation of CSIR further depleted GSH through reactive oxygen species (ROS) generation. Additionally, CSIR released sorafenib (SRF), which inhibited cystine-glutamate antiporter system xCT (xCT), thereby blocking GSH biosynthesis. RNA sequencing data confirmed ferroptosis induction by CSIR. This synergistic strategy of GSH depletion-induced ferroptosis, enhanced PDT, and photothermal cascade holds promise for improved osteosarcoma treatment and future nanomedicine design. |
| format | Article |
| id | doaj-art-b0be5852ba6b4985b68e99b9d2eea70d |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-b0be5852ba6b4985b68e99b9d2eea70d2025-08-20T03:52:24ZengBMCJournal of Nanobiotechnology1477-31552025-04-0123111710.1186/s12951-025-03380-4A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapyTangbing Xu0Qiming Ma1Chi Zhang2Xiaoyan He3Qian Wang4Yunfeng Wu5Kunpeng Qin6Faxue Liao7Ping Zhou8Pengfei Xu9Jialai Yang10Junjun Yang11Jun Chang12Lei Qiao13Yong Hu14Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversitySchool of Life Sciences, Anhui Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityAnhui Public Health Clinical CenterDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Polymer Science and Engineering, University of Science and Technology of ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Anhui Medical UniversityAbstract Osteosarcoma treatment remains challenging due to the limitations of single-modality therapies. To address this, we designed a carrier-free nanomedicine SRF@CuSO4.5H2O@IR780 (CSIR) for synergistic ferroptosis, photodynamic therapy (PDT), and photothermal therapy (PTT) in osteosarcoma. Interestingly, CSIR could harness the enhanced permeability and retention (EPR) effect to effectively enter tumors. Copper ions (Cu2+) within CSIR could react with the reductive intracellular environment, depleting glutathione (GSH) levels. Near-infrared (NIR) irradiation of CSIR further depleted GSH through reactive oxygen species (ROS) generation. Additionally, CSIR released sorafenib (SRF), which inhibited cystine-glutamate antiporter system xCT (xCT), thereby blocking GSH biosynthesis. RNA sequencing data confirmed ferroptosis induction by CSIR. This synergistic strategy of GSH depletion-induced ferroptosis, enhanced PDT, and photothermal cascade holds promise for improved osteosarcoma treatment and future nanomedicine design.https://doi.org/10.1186/s12951-025-03380-4Carrier-free nanomedicineOsteosarcomaFerroptosisPDT/PTT TherapyReactive oxygen species |
| spellingShingle | Tangbing Xu Qiming Ma Chi Zhang Xiaoyan He Qian Wang Yunfeng Wu Kunpeng Qin Faxue Liao Ping Zhou Pengfei Xu Jialai Yang Junjun Yang Jun Chang Lei Qiao Yong Hu A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapy Journal of Nanobiotechnology Carrier-free nanomedicine Osteosarcoma Ferroptosis PDT/PTT Therapy Reactive oxygen species |
| title | A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapy |
| title_full | A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapy |
| title_fullStr | A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapy |
| title_full_unstemmed | A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapy |
| title_short | A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapy |
| title_sort | novel nanomedicine for osteosarcoma treatment triggering ferroptosis through gsh depletion and inhibition for enhanced synergistic pdt ptt therapy |
| topic | Carrier-free nanomedicine Osteosarcoma Ferroptosis PDT/PTT Therapy Reactive oxygen species |
| url | https://doi.org/10.1186/s12951-025-03380-4 |
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