Au6Cu2 Clusters with High Electron Affinity and Oxygen-Mimetic Properties for Hypoxic Tumor Radiosensitization
Dr. Xueli Zhao
Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Henan International Joint Laboratory of Tumor Theranostic Cluster Materials, College of Chemistry, Zhengzhou University, Zhengzhou, China
Both authors contributed equally to this work.
Search for more papers by this authorJingpeng Han
Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Henan International Joint Laboratory of Tumor Theranostic Cluster Materials, College of Chemistry, Zhengzhou University, Zhengzhou, China
Both authors contributed equally to this work.
Search for more papers by this authorDr. Junqi Liu
The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000 China
Search for more papers by this authorProf. Zhao-Yang Wang
Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Henan International Joint Laboratory of Tumor Theranostic Cluster Materials, College of Chemistry, Zhengzhou University, Zhengzhou, China
Search for more papers by this authorCorresponding Author
Prof. Xiaoyuan Chen
Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074 Singapore
Department of Chemical and Biomolecular Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117575 Singapore
Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117575 Singapore
Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore, 117544 Singapore
Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599 Singapore
Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597 Singapore
Theranostics Center of Excellence (TCE), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 138667 Singapore
Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore, 138673 Singapore
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Shuang-Quan Zang
Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Henan International Joint Laboratory of Tumor Theranostic Cluster Materials, College of Chemistry, Zhengzhou University, Zhengzhou, China
E-mail: [email protected]; [email protected]
Search for more papers by this authorDr. Xueli Zhao
Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Henan International Joint Laboratory of Tumor Theranostic Cluster Materials, College of Chemistry, Zhengzhou University, Zhengzhou, China
Both authors contributed equally to this work.
Search for more papers by this authorJingpeng Han
Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Henan International Joint Laboratory of Tumor Theranostic Cluster Materials, College of Chemistry, Zhengzhou University, Zhengzhou, China
Both authors contributed equally to this work.
Search for more papers by this authorDr. Junqi Liu
The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000 China
Search for more papers by this authorProf. Zhao-Yang Wang
Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Henan International Joint Laboratory of Tumor Theranostic Cluster Materials, College of Chemistry, Zhengzhou University, Zhengzhou, China
Search for more papers by this authorCorresponding Author
Prof. Xiaoyuan Chen
Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074 Singapore
Department of Chemical and Biomolecular Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117575 Singapore
Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117575 Singapore
Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore, 117544 Singapore
Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599 Singapore
Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597 Singapore
Theranostics Center of Excellence (TCE), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 138667 Singapore
Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore, 138673 Singapore
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Shuang-Quan Zang
Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Henan International Joint Laboratory of Tumor Theranostic Cluster Materials, College of Chemistry, Zhengzhou University, Zhengzhou, China
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
Hypoxia-induced radioresistance primarily contributes to the failure of radiotherapy because it hinders the effective fixation of DNA damage. Despite the considerable antitumor activity of chemical molecules such as electron-affinic nitroimidazoles affirmed by clinical studies, their dose-dependent side effects and low radiotherapy efficacy have become major drawbacks. In this study, we synthesized nitrobenzene-functionalized Au6Cu2 (NO2-Au6Cu2) clusters, integrating metal clusters with chemical radiosensitizers. The ligand 4-nitrophenylacetylene's hypoxia-selective toxicity arises from reductase-mediated radical generation under hypoxia, depleting GSH and compromising radiotherapy ROS clearance. Our findings indicate that the electron affinity of interfacial ligands has a significant effect on the electron affinity and hypoxic cytotoxicity of metal clusters. Experimental results demonstrated that NO2-Au6Cu2 clusters exhibit a high sensitization enhancement ratio by leveraging the properties of gold clusters to augment radiotherapy and the oxygen-mimetic property of chemical molecules to impair DNA repair pathways. This research introduces a novel strategy for developing highly efficient metal cluster-based hypoxic radiosensitizers.
Conflict of Interests
X.C. is a co-founder of and holds shares in Yantai Lannacheng Biotechnology Co., Ltd.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the Supporting Information of this article.
Supporting Information
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| ange202504524-supp-0001-SuppMat.docx35 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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