Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy
Acute kidney injury (AKI) induced by cisplatin (DDP), which is accompanied with the generation of reactive oxygen species (ROS), is a severe side effect during treatment and restricts the application of DDP. In this study, we develop ultrasmall Mn3O4 nanozyme (UMON) with tumor microenvironment (TME)...
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Elsevier
2024-12-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424003892 |
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| author | Yanan Ren Fei Wu Linlin Huo Xiao Wang Yong Zhang Mengke Fan Mingya Tan Jiayi Zhao Jingliang Cheng Zhenghuan Zhao Jianfeng Bao |
| author_facet | Yanan Ren Fei Wu Linlin Huo Xiao Wang Yong Zhang Mengke Fan Mingya Tan Jiayi Zhao Jingliang Cheng Zhenghuan Zhao Jianfeng Bao |
| author_sort | Yanan Ren |
| collection | DOAJ |
| description | Acute kidney injury (AKI) induced by cisplatin (DDP), which is accompanied with the generation of reactive oxygen species (ROS), is a severe side effect during treatment and restricts the application of DDP. In this study, we develop ultrasmall Mn3O4 nanozyme (UMON) with tumor microenvironment (TME) responsive ROS scavenging and generating as adjuvant to alleviate DDP induced AKI with improved efficacy. In kidney, UMON with superoxide dismutase and catalase activity acts as ROS scavenger to eliminate ROS generated by DDP, successfully protecting the renal cells/tissue and alleviating AKI during DDP treatment. Alternatively, UMON rapidly responses to the high GSH level in TME and release Mn2+ in tumor. This unique feature endows it to generate hydroxyl radicals (∙OH) through a Fenton-like reaction and deplete GSH in tumor cell and tissue, achieving high efficient chemodynamic therapy (CDT). More importantly, the Mn2+ successfully activates the cGAS-STING pathway, initiating the immune response and effectively inhibiting the tumor metastases. The synergistic CDT and immune therapy effectively improve the anti-tumor efficacy of DDP in vitro and in vivo. This study demonstrates that TME responsive ROS scavenger/generator shows the potential to reduce side effects of DDP while improve its therapeutic efficacy, providing a new avenue to achieve efficient chemotherapy and promoting the progress of clinical chemotherapy. |
| format | Article |
| id | doaj-art-5320faec67b949fb9d8052f4f5c4a7c9 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-5320faec67b949fb9d8052f4f5c4a7c92024-12-14T06:32:18ZengElsevierMaterials Today Bio2590-00642024-12-0129101328Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapyYanan Ren0Fei Wu1Linlin Huo2Xiao Wang3Yong Zhang4Mengke Fan5Mingya Tan6Jiayi Zhao7Jingliang Cheng8Zhenghuan Zhao9Jianfeng Bao10Functional Magnetic Resonance and Molecular Imaging Key Laboratory of Henan Province, Department of Magnetic Resonance Imaging, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, ChinaFunctional Magnetic Resonance and Molecular Imaging Key Laboratory of Henan Province, Department of Magnetic Resonance Imaging, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, ChinaCollege of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaFunctional Magnetic Resonance and Molecular Imaging Key Laboratory of Henan Province, Department of Magnetic Resonance Imaging, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, ChinaFunctional Magnetic Resonance and Molecular Imaging Key Laboratory of Henan Province, Department of Magnetic Resonance Imaging, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, ChinaCollege of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaCollege of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaCollege of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaFunctional Magnetic Resonance and Molecular Imaging Key Laboratory of Henan Province, Department of Magnetic Resonance Imaging, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, China; Corresponding author.College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China; Corresponding author.Functional Magnetic Resonance and Molecular Imaging Key Laboratory of Henan Province, Department of Magnetic Resonance Imaging, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, China; Corresponding author.Acute kidney injury (AKI) induced by cisplatin (DDP), which is accompanied with the generation of reactive oxygen species (ROS), is a severe side effect during treatment and restricts the application of DDP. In this study, we develop ultrasmall Mn3O4 nanozyme (UMON) with tumor microenvironment (TME) responsive ROS scavenging and generating as adjuvant to alleviate DDP induced AKI with improved efficacy. In kidney, UMON with superoxide dismutase and catalase activity acts as ROS scavenger to eliminate ROS generated by DDP, successfully protecting the renal cells/tissue and alleviating AKI during DDP treatment. Alternatively, UMON rapidly responses to the high GSH level in TME and release Mn2+ in tumor. This unique feature endows it to generate hydroxyl radicals (∙OH) through a Fenton-like reaction and deplete GSH in tumor cell and tissue, achieving high efficient chemodynamic therapy (CDT). More importantly, the Mn2+ successfully activates the cGAS-STING pathway, initiating the immune response and effectively inhibiting the tumor metastases. The synergistic CDT and immune therapy effectively improve the anti-tumor efficacy of DDP in vitro and in vivo. This study demonstrates that TME responsive ROS scavenger/generator shows the potential to reduce side effects of DDP while improve its therapeutic efficacy, providing a new avenue to achieve efficient chemotherapy and promoting the progress of clinical chemotherapy.http://www.sciencedirect.com/science/article/pii/S2590006424003892Switchable ROS scavenger/generatorCisplatin adjuvantAcute kidney injuryImproved therapeutic efficacy |
| spellingShingle | Yanan Ren Fei Wu Linlin Huo Xiao Wang Yong Zhang Mengke Fan Mingya Tan Jiayi Zhao Jingliang Cheng Zhenghuan Zhao Jianfeng Bao Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy Materials Today Bio Switchable ROS scavenger/generator Cisplatin adjuvant Acute kidney injury Improved therapeutic efficacy |
| title | Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy |
| title_full | Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy |
| title_fullStr | Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy |
| title_full_unstemmed | Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy |
| title_short | Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy |
| title_sort | switchable ros generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic immune therapy |
| topic | Switchable ROS scavenger/generator Cisplatin adjuvant Acute kidney injury Improved therapeutic efficacy |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424003892 |
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