Construction of Active Sites‐Accessible Au8 Clusters for Intensive Tumor Pyroptosis

ABSTRACT Atomically precise gold nanoclusters (NCs), possessing characteristics of molecules and nanoparticles, offer a promising solution to the challenges faced by existing pyroptosis inducers. Their abilities to catalyze the generation of reactive oxygen species and enhance radiosensitization pos...

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Main Authors: Qiu‐Xu Zang, Wei‐Tong Chen, Wenjing Zhang, Zhao‐Yang Wang, Xi‐Yan Dong, Runping Han, Yanjuan Sang, Xiaoyuan Chen, Shuang‐Quan Zang
Format: Article
Language:English
Published: Wiley 2025-06-01
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Online Access:https://doi.org/10.1002/agt2.70046
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author Qiu‐Xu Zang
Wei‐Tong Chen
Wenjing Zhang
Zhao‐Yang Wang
Xi‐Yan Dong
Runping Han
Yanjuan Sang
Xiaoyuan Chen
Shuang‐Quan Zang
author_facet Qiu‐Xu Zang
Wei‐Tong Chen
Wenjing Zhang
Zhao‐Yang Wang
Xi‐Yan Dong
Runping Han
Yanjuan Sang
Xiaoyuan Chen
Shuang‐Quan Zang
author_sort Qiu‐Xu Zang
collection DOAJ
description ABSTRACT Atomically precise gold nanoclusters (NCs), possessing characteristics of molecules and nanoparticles, offer a promising solution to the challenges faced by existing pyroptosis inducers. Their abilities to catalyze the generation of reactive oxygen species and enhance radiosensitization position them as effective agents for activating pyroptosis. However, their catalytic efficiency is often compromised by limited geometrically accessible spaces around the active sites and the lack of suitable ligands. Leveraging the exposed metal centers in mononuclear organometallic catalysts and the tunable ligand of NCs, herein, ethynylferrocene (EFc) was utilized to amplify the peroxidase (POD)‐like activity of gold NCs by establishing the unshielded catalytic center and electron donor‐acceptor interaction between EFc and Au core. The resulting Au8Fe2 NCs with excellent POD‐mimicking activity could efficiently trigger pyroptosis by inducing intracellular oxidative stress. Moreover, the Au8Fe2 NCs, with their potential to deplete glutathione and enable magnetic resonance imaging, could also induce ferroptosis and serve as a diagnostic tool for tumors. All of these processes can be further potentiated by X‐ray radiation, taking advantage of the high atomic number of gold. This work opens new avenues for engineering the catalytic properties of NCs and broadens their potential applications in biomedicine.
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spelling doaj-art-aa4d1b35cbac4fbe80e6639e05e3ff6c2025-08-20T03:22:45ZengWileyAggregate2692-45602025-06-0166n/an/a10.1002/agt2.70046Construction of Active Sites‐Accessible Au8 Clusters for Intensive Tumor PyroptosisQiu‐Xu Zang0Wei‐Tong Chen1Wenjing Zhang2Zhao‐Yang Wang3Xi‐Yan Dong4Runping Han5Yanjuan Sang6Xiaoyuan Chen7Shuang‐Quan Zang8Tianjian 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 ChinaTianjian 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 ChinaTianjian 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 ChinaTianjian 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 ChinaTianjian 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 ChinaTianjian 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 ChinaTianjian 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 ChinaDepartment of Diagnostic Radiology, Yong Loo Lin School of Medicine National University of Singapore Singapore SingaporeTianjian 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 ChinaABSTRACT Atomically precise gold nanoclusters (NCs), possessing characteristics of molecules and nanoparticles, offer a promising solution to the challenges faced by existing pyroptosis inducers. Their abilities to catalyze the generation of reactive oxygen species and enhance radiosensitization position them as effective agents for activating pyroptosis. However, their catalytic efficiency is often compromised by limited geometrically accessible spaces around the active sites and the lack of suitable ligands. Leveraging the exposed metal centers in mononuclear organometallic catalysts and the tunable ligand of NCs, herein, ethynylferrocene (EFc) was utilized to amplify the peroxidase (POD)‐like activity of gold NCs by establishing the unshielded catalytic center and electron donor‐acceptor interaction between EFc and Au core. The resulting Au8Fe2 NCs with excellent POD‐mimicking activity could efficiently trigger pyroptosis by inducing intracellular oxidative stress. Moreover, the Au8Fe2 NCs, with their potential to deplete glutathione and enable magnetic resonance imaging, could also induce ferroptosis and serve as a diagnostic tool for tumors. All of these processes can be further potentiated by X‐ray radiation, taking advantage of the high atomic number of gold. This work opens new avenues for engineering the catalytic properties of NCs and broadens their potential applications in biomedicine.https://doi.org/10.1002/agt2.70046catalytic performance | ferrocene | gold nanocluster | ligand engineering | pyroptosis
spellingShingle Qiu‐Xu Zang
Wei‐Tong Chen
Wenjing Zhang
Zhao‐Yang Wang
Xi‐Yan Dong
Runping Han
Yanjuan Sang
Xiaoyuan Chen
Shuang‐Quan Zang
Construction of Active Sites‐Accessible Au8 Clusters for Intensive Tumor Pyroptosis
Aggregate
catalytic performance | ferrocene | gold nanocluster | ligand engineering | pyroptosis
title Construction of Active Sites‐Accessible Au8 Clusters for Intensive Tumor Pyroptosis
title_full Construction of Active Sites‐Accessible Au8 Clusters for Intensive Tumor Pyroptosis
title_fullStr Construction of Active Sites‐Accessible Au8 Clusters for Intensive Tumor Pyroptosis
title_full_unstemmed Construction of Active Sites‐Accessible Au8 Clusters for Intensive Tumor Pyroptosis
title_short Construction of Active Sites‐Accessible Au8 Clusters for Intensive Tumor Pyroptosis
title_sort construction of active sites accessible au8 clusters for intensive tumor pyroptosis
topic catalytic performance | ferrocene | gold nanocluster | ligand engineering | pyroptosis
url https://doi.org/10.1002/agt2.70046
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