PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapy
Nanozymes constitute a promising treatment strategy for antitumor therapy. However, the catalytic function of metal‒organic framework (MOF)-based nanozymes during cuproptosis remains unclear. In this study, a Cu(Ⅱ)-based MOF nanocomposite loaded with the copper ionophore elesclomol and surface modif...
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Elsevier
2024-12-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424003788 |
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| author | Xufeng Lu Wenhai Deng Shuaibin Wang Shengsheng Zhao Bingzi Zhu Binglong Bai Yiwen Mao Ji Lin Yongdong Yi Zuoliang Xie Xiang Wang Yongyong Lu Xiufeng Huang Tao You Xiaolei Chen Weijian Sun Xian Shen |
| author_facet | Xufeng Lu Wenhai Deng Shuaibin Wang Shengsheng Zhao Bingzi Zhu Binglong Bai Yiwen Mao Ji Lin Yongdong Yi Zuoliang Xie Xiang Wang Yongyong Lu Xiufeng Huang Tao You Xiaolei Chen Weijian Sun Xian Shen |
| author_sort | Xufeng Lu |
| collection | DOAJ |
| description | Nanozymes constitute a promising treatment strategy for antitumor therapy. However, the catalytic function of metal‒organic framework (MOF)-based nanozymes during cuproptosis remains unclear. In this study, a Cu(Ⅱ)-based MOF nanocomposite loaded with the copper ionophore elesclomol and surface modified with polyethylene glycol polymer (PEG) was developed (ES@Cu(Ⅱ)-MOF) for effective cuproptosis induction. The peroxidase (POD)-like activity of ES@Cu(Ⅱ)-MOF generated an abundance of hydroxyl radicals (•OH) via a Fenton-like reaction, and its glutathione peroxidase (GSH-Px)-like activity converted Cu2+ into more toxic Cu+ ions to efficiently consume endogenous GSH. Notably, the rapid accumulation of Cu+ and ES in tumor cells induced the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and the downregulation of Fe‒S cluster proteins, ultimately leading to cuproptosis. ES@Cu(Ⅱ)-MOF exhibited extraordinary cytotoxicity against breast cancer cells in vitro and significantly suppressed 4T1 breast tumor growth in vivo. Moreover, ES@Cu(Ⅱ)-MOF induced immunogenic cell death (ICD) to increase the antitumor immune response. Furthermore, combining ES@Cu(Ⅱ)-MOF with an anti-programmed cell death-ligand 1 (PD-L1) antibody converted the immunosuppressive tumor microenvironment to an immunogenic microenvironment, thus effectively inhibiting breast tumor growth. Overall, this work provides an innovative approach utilizing nanozymes to facilitate cuproptosis for cancer treatment, which potentially enhances the effectiveness of immune checkpoint inhibitor-based immunotherapy. |
| format | Article |
| id | doaj-art-00404f8a0cfc418897fd34b532ce7343 |
| institution | DOAJ |
| issn | 2590-0064 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-00404f8a0cfc418897fd34b532ce73432025-08-20T02:39:31ZengElsevierMaterials Today Bio2590-00642024-12-012910131710.1016/j.mtbio.2024.101317PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapyXufeng Lu0Wenhai Deng1Shuaibin Wang2Shengsheng Zhao3Bingzi Zhu4Binglong Bai5Yiwen Mao6Ji Lin7Yongdong Yi8Zuoliang Xie9Xiang Wang10Yongyong Lu11Xiufeng Huang12Tao You13Xiaolei Chen14Weijian Sun15Xian Shen16Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Research Center of Basic Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaDepartment of Breast Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaResearch Center of Basic Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Corresponding author.Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Corresponding author. Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Corresponding author. Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.Nanozymes constitute a promising treatment strategy for antitumor therapy. However, the catalytic function of metal‒organic framework (MOF)-based nanozymes during cuproptosis remains unclear. In this study, a Cu(Ⅱ)-based MOF nanocomposite loaded with the copper ionophore elesclomol and surface modified with polyethylene glycol polymer (PEG) was developed (ES@Cu(Ⅱ)-MOF) for effective cuproptosis induction. The peroxidase (POD)-like activity of ES@Cu(Ⅱ)-MOF generated an abundance of hydroxyl radicals (•OH) via a Fenton-like reaction, and its glutathione peroxidase (GSH-Px)-like activity converted Cu2+ into more toxic Cu+ ions to efficiently consume endogenous GSH. Notably, the rapid accumulation of Cu+ and ES in tumor cells induced the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and the downregulation of Fe‒S cluster proteins, ultimately leading to cuproptosis. ES@Cu(Ⅱ)-MOF exhibited extraordinary cytotoxicity against breast cancer cells in vitro and significantly suppressed 4T1 breast tumor growth in vivo. Moreover, ES@Cu(Ⅱ)-MOF induced immunogenic cell death (ICD) to increase the antitumor immune response. Furthermore, combining ES@Cu(Ⅱ)-MOF with an anti-programmed cell death-ligand 1 (PD-L1) antibody converted the immunosuppressive tumor microenvironment to an immunogenic microenvironment, thus effectively inhibiting breast tumor growth. Overall, this work provides an innovative approach utilizing nanozymes to facilitate cuproptosis for cancer treatment, which potentially enhances the effectiveness of immune checkpoint inhibitor-based immunotherapy.http://www.sciencedirect.com/science/article/pii/S2590006424003788Cu(Ⅱ)-MOFNanozymeCuproptosisBreast cancerAnti-PD-L1 antibodyImmunotherapy |
| spellingShingle | Xufeng Lu Wenhai Deng Shuaibin Wang Shengsheng Zhao Bingzi Zhu Binglong Bai Yiwen Mao Ji Lin Yongdong Yi Zuoliang Xie Xiang Wang Yongyong Lu Xiufeng Huang Tao You Xiaolei Chen Weijian Sun Xian Shen PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapy Materials Today Bio Cu(Ⅱ)-MOF Nanozyme Cuproptosis Breast cancer Anti-PD-L1 antibody Immunotherapy |
| title | PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapy |
| title_full | PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapy |
| title_fullStr | PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapy |
| title_full_unstemmed | PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapy |
| title_short | PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapy |
| title_sort | pegylated elesclomol cu ii based metal organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced pd l1 based immunotherapy |
| topic | Cu(Ⅱ)-MOF Nanozyme Cuproptosis Breast cancer Anti-PD-L1 antibody Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424003788 |
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