Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy

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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Bibliographic Details
Main Authors: Yanan Ren, Fei Wu, Linlin Huo, Xiao Wang, Yong Zhang, Mengke Fan, Mingya Tan, Jiayi Zhao, Jingliang Cheng, Zhenghuan Zhao, Jianfeng Bao
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Materials Today Bio
Subjects:
Switchable ROS scavenger/generator
Cisplatin adjuvant
Acute kidney injury
Improved therapeutic efficacy
Online Access:http://www.sciencedirect.com/science/article/pii/S2590006424003892
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Summary: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.
ISSN:2590-0064

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