Bimetallic clusterzymes-loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ROS scavenging and YAP1 stabilization
Clusterzymes are synthetic enzymes exhibiting substantial catalytic activity and selectivity, which are uniquely driven by single-atom constructs. A dramatic increase in antioxidant capacity, 158 times more than natural trolox, is noted when single-atom copper is incorporated into gold-based cluster...
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KeAi Communications Co., Ltd.
2024-12-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24003918 |
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| author | Yang Jin Chuan Hu Jiechao Xia Dingqi Xie Lin Ye Xinyi Ye Li Jiang Honghai Song Yutao Zhu Sicheng Jiang Weiqing Li Weiming Qi Yannan Yang Zhijun Hu |
| author_facet | Yang Jin Chuan Hu Jiechao Xia Dingqi Xie Lin Ye Xinyi Ye Li Jiang Honghai Song Yutao Zhu Sicheng Jiang Weiqing Li Weiming Qi Yannan Yang Zhijun Hu |
| author_sort | Yang Jin |
| collection | DOAJ |
| description | Clusterzymes are synthetic enzymes exhibiting substantial catalytic activity and selectivity, which are uniquely driven by single-atom constructs. A dramatic increase in antioxidant capacity, 158 times more than natural trolox, is noted when single-atom copper is incorporated into gold-based clusterzymes to form Au24Cu1. Considering the inflammatory and mildly acidic microenvironment characteristic of osteoarthritis (OA), pH-dependent dendritic mesoporous silica nanoparticles (DMSNs) coupled with PEG have been employed as a delivery system for the spatial-temporal release of clusterzymes within active articular regions, thereby enhancing the duration of effectiveness. Nonetheless, achieving high therapeutic efficacy remains a significant challenge. Herein, we describe the construction of a Clusterzymes-DMSNs-PEG complex (CDP) which remarkably diminishes reactive oxygen species (ROS) and stabilizes the chondroprotective protein YAP by inhibiting the Hippo pathway. In the rabbit ACLT (anterior cruciate ligament transection) model, the CDP complex demonstrated inhibition of matrix metalloproteinase activity, preservation of type II collagen and aggregation protein secretion, thus prolonging the clusterzymes' protective influence on joint cartilage structure. Our research underscores the efficacy of the CDP complex in ROS-scavenging, enabled by the release of clusterzymes in response to an inflammatory and slightly acidic environment, leading to the obstruction of the Hippo pathway and downstream NF-κB signaling pathway. This study illuminates the design, composition, and use of DMSNs and clusterzymes in biomedicine, thus charting a promising course for the development of novel therapeutic strategies in alleviating OA. |
| format | Article |
| id | doaj-art-4d1ad7d4e19e4b4888c1d4aa08dae15a |
| institution | OA Journals |
| issn | 2452-199X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Bioactive Materials |
| spelling | doaj-art-4d1ad7d4e19e4b4888c1d4aa08dae15a2025-08-20T02:18:46ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-12-014261362710.1016/j.bioactmat.2024.09.004Bimetallic clusterzymes-loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ROS scavenging and YAP1 stabilizationYang Jin0Chuan Hu1Jiechao Xia2Dingqi Xie3Lin Ye4Xinyi Ye5Li Jiang6Honghai Song7Yutao Zhu8Sicheng Jiang9Weiqing Li10Weiming Qi11Yannan Yang12Zhijun Hu13Department of Orthopaedic Surgery, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, ChinaDepartment of Orthopaedic Surgery, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, ChinaDepartment of Orthopaedic Surgery, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, ChinaDepartment of Orthopaedic Surgery, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, ChinaDepartment of Orthopaedic Surgery, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, ChinaZhejiang University School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, ChinaDepartment of Orthopaedic Surgery, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, ChinaDepartment of Orthopaedic Surgery, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, ChinaDepartment of Orthopaedic Surgery, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, ChinaZhejiang University School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Center for Medical Device Evaluation, Zhejiang Medical Products Administration Hangzhou 310009, Zhejiang, China; Corresponding author. Zhejiang Center for Medical Device Evaluation, Zhejiang Medical Products Administration Hangzhou 310009, Zhejiang, China.Institute of Optoelectronics, Fudan University, Shanghai, 200433, China; South Australian ImmunoGENomics Cancer Institute, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, 5005, Australia; Corresponding author. South Australian ImmunoGENomics Cancer Institute, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, 5005, Australia.Department of Orthopaedic Surgery, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, China; Corresponding author.Clusterzymes are synthetic enzymes exhibiting substantial catalytic activity and selectivity, which are uniquely driven by single-atom constructs. A dramatic increase in antioxidant capacity, 158 times more than natural trolox, is noted when single-atom copper is incorporated into gold-based clusterzymes to form Au24Cu1. Considering the inflammatory and mildly acidic microenvironment characteristic of osteoarthritis (OA), pH-dependent dendritic mesoporous silica nanoparticles (DMSNs) coupled with PEG have been employed as a delivery system for the spatial-temporal release of clusterzymes within active articular regions, thereby enhancing the duration of effectiveness. Nonetheless, achieving high therapeutic efficacy remains a significant challenge. Herein, we describe the construction of a Clusterzymes-DMSNs-PEG complex (CDP) which remarkably diminishes reactive oxygen species (ROS) and stabilizes the chondroprotective protein YAP by inhibiting the Hippo pathway. In the rabbit ACLT (anterior cruciate ligament transection) model, the CDP complex demonstrated inhibition of matrix metalloproteinase activity, preservation of type II collagen and aggregation protein secretion, thus prolonging the clusterzymes' protective influence on joint cartilage structure. Our research underscores the efficacy of the CDP complex in ROS-scavenging, enabled by the release of clusterzymes in response to an inflammatory and slightly acidic environment, leading to the obstruction of the Hippo pathway and downstream NF-κB signaling pathway. This study illuminates the design, composition, and use of DMSNs and clusterzymes in biomedicine, thus charting a promising course for the development of novel therapeutic strategies in alleviating OA.http://www.sciencedirect.com/science/article/pii/S2452199X24003918ClusterzymeSustained deliveryReactive oxygen speciesHippo pathwayRabbit anterior cruciate ligament transection model |
| spellingShingle | Yang Jin Chuan Hu Jiechao Xia Dingqi Xie Lin Ye Xinyi Ye Li Jiang Honghai Song Yutao Zhu Sicheng Jiang Weiqing Li Weiming Qi Yannan Yang Zhijun Hu Bimetallic clusterzymes-loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ROS scavenging and YAP1 stabilization Bioactive Materials Clusterzyme Sustained delivery Reactive oxygen species Hippo pathway Rabbit anterior cruciate ligament transection model |
| title | Bimetallic clusterzymes-loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ROS scavenging and YAP1 stabilization |
| title_full | Bimetallic clusterzymes-loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ROS scavenging and YAP1 stabilization |
| title_fullStr | Bimetallic clusterzymes-loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ROS scavenging and YAP1 stabilization |
| title_full_unstemmed | Bimetallic clusterzymes-loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ROS scavenging and YAP1 stabilization |
| title_short | Bimetallic clusterzymes-loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ROS scavenging and YAP1 stabilization |
| title_sort | bimetallic clusterzymes loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ros scavenging and yap1 stabilization |
| topic | Clusterzyme Sustained delivery Reactive oxygen species Hippo pathway Rabbit anterior cruciate ligament transection model |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24003918 |
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