Synergistic SDT/cuproptosis therapy for liver hepatocellular carcinoma: enhanced antitumor efficacy and specific mechanisms
Abstract The efficacy of sonodynamic therapy (SDT), an emerging approach for tumor treatment, is hindered by the high levels of the antioxidant glutathione (GSH) in the tumor microenvironment (TME). In this study, we constructed nanobubbles loaded with the sonosensitizer HMME and the tumor-targeting...
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| Language: | English |
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BMC
2024-12-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-02995-3 |
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| author | Yucao Sun Yichi Chen Bolin Wu Helin Li Yijun Wang Xiaodong Wang Liwen Deng Kuikun Yang Xiuhong Wang Wen Cheng |
| author_facet | Yucao Sun Yichi Chen Bolin Wu Helin Li Yijun Wang Xiaodong Wang Liwen Deng Kuikun Yang Xiuhong Wang Wen Cheng |
| author_sort | Yucao Sun |
| collection | DOAJ |
| description | Abstract The efficacy of sonodynamic therapy (SDT), an emerging approach for tumor treatment, is hindered by the high levels of the antioxidant glutathione (GSH) in the tumor microenvironment (TME). In this study, we constructed nanobubbles loaded with the sonosensitizer HMME and the tumor-targeting peptide RGD (HMME-RGD@C3F8 NBs) for synergistic SDT/cuproptosis therapy of liver hepatocellular carcinoma (LIHC) in combination with Elesclomol-Cu as cuproptosis inducers. Endogenous GSH is consumed by Cu2+ to modulate the complex TME, thereby amplifying oxidative stress and further improving SDT performance. Additionally, intracellular Cu2+ overload can induce cuproptosis, which is further amplified by SDT, to initiate irreversible protein toxicity. The specific mechanism of synergistic SDT/cuproptosis therapy in LIHC was investigated by RNA sequencing analysis. The synergistic SDT/cuproptosis therapy reprogrammed the TME to improve the efficacy of immune checkpoint inhibitor-based immunotherapy. Furthermore, a risk-scoring model was created and displayed significant promise in the prognosis of LIHC. Graphical Abstract |
| format | Article |
| id | doaj-art-b27aa57a9f9744ac954b21d79d02e433 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-b27aa57a9f9744ac954b21d79d02e4332025-08-20T01:57:12ZengBMCJournal of Nanobiotechnology1477-31552024-12-0122111810.1186/s12951-024-02995-3Synergistic SDT/cuproptosis therapy for liver hepatocellular carcinoma: enhanced antitumor efficacy and specific mechanismsYucao Sun0Yichi Chen1Bolin Wu2Helin Li3Yijun Wang4Xiaodong Wang5Liwen Deng6Kuikun Yang7Xiuhong Wang8Wen Cheng9Department of Ultrasound, Department of Interventional Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Department of Interventional Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Department of Interventional Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Department of Interventional Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Department of Interventional Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Department of Interventional Ultrasound, Harbin Medical University Cancer HospitalDepartment of Ultrasound, Department of Interventional Ultrasound, Harbin Medical University Cancer HospitalSchool of Life Science and Technology, Harbin Institute of TechnologyDepartment of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical UniversityDepartment of Ultrasound, Department of Interventional Ultrasound, Harbin Medical University Cancer HospitalAbstract The efficacy of sonodynamic therapy (SDT), an emerging approach for tumor treatment, is hindered by the high levels of the antioxidant glutathione (GSH) in the tumor microenvironment (TME). In this study, we constructed nanobubbles loaded with the sonosensitizer HMME and the tumor-targeting peptide RGD (HMME-RGD@C3F8 NBs) for synergistic SDT/cuproptosis therapy of liver hepatocellular carcinoma (LIHC) in combination with Elesclomol-Cu as cuproptosis inducers. Endogenous GSH is consumed by Cu2+ to modulate the complex TME, thereby amplifying oxidative stress and further improving SDT performance. Additionally, intracellular Cu2+ overload can induce cuproptosis, which is further amplified by SDT, to initiate irreversible protein toxicity. The specific mechanism of synergistic SDT/cuproptosis therapy in LIHC was investigated by RNA sequencing analysis. The synergistic SDT/cuproptosis therapy reprogrammed the TME to improve the efficacy of immune checkpoint inhibitor-based immunotherapy. Furthermore, a risk-scoring model was created and displayed significant promise in the prognosis of LIHC. Graphical Abstracthttps://doi.org/10.1186/s12951-024-02995-3CuproptosisSonodynamic therapyLiver hepatocellular carcinomaSynergistic tumor therapyRNA sequencing |
| spellingShingle | Yucao Sun Yichi Chen Bolin Wu Helin Li Yijun Wang Xiaodong Wang Liwen Deng Kuikun Yang Xiuhong Wang Wen Cheng Synergistic SDT/cuproptosis therapy for liver hepatocellular carcinoma: enhanced antitumor efficacy and specific mechanisms Journal of Nanobiotechnology Cuproptosis Sonodynamic therapy Liver hepatocellular carcinoma Synergistic tumor therapy RNA sequencing |
| title | Synergistic SDT/cuproptosis therapy for liver hepatocellular carcinoma: enhanced antitumor efficacy and specific mechanisms |
| title_full | Synergistic SDT/cuproptosis therapy for liver hepatocellular carcinoma: enhanced antitumor efficacy and specific mechanisms |
| title_fullStr | Synergistic SDT/cuproptosis therapy for liver hepatocellular carcinoma: enhanced antitumor efficacy and specific mechanisms |
| title_full_unstemmed | Synergistic SDT/cuproptosis therapy for liver hepatocellular carcinoma: enhanced antitumor efficacy and specific mechanisms |
| title_short | Synergistic SDT/cuproptosis therapy for liver hepatocellular carcinoma: enhanced antitumor efficacy and specific mechanisms |
| title_sort | synergistic sdt cuproptosis therapy for liver hepatocellular carcinoma enhanced antitumor efficacy and specific mechanisms |
| topic | Cuproptosis Sonodynamic therapy Liver hepatocellular carcinoma Synergistic tumor therapy RNA sequencing |
| url | https://doi.org/10.1186/s12951-024-02995-3 |
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