Polyacrylic Acid-Coated Selenium-Doped Carbon Dots Inhibit Ferroptosis to Alleviate Chemotherapy-Associated Acute Kidney Injury
文献类型： 外文期刊
作者： Li, Jiahuan 1 ; Fu, Chengcheng 3 ; Feng, Baoli 1 ; Liu, Qingquan 7 ; Gu, Jiangjiang 8 ; Khan, Mohammad Nauman 9 ; Sun, Lvhui 1 ; Wu, Honghong 2 ; Wu, Hao 1 ;
作者机构： 1.Huazhong Agr Univ, Coll Anim Sci & Technol, State Key Lab Agr Microbiol, Wuhan 430070, Peoples R China
2.Huazhong Agr Univ, Coll Vet Med, Wuhan 430070, Peoples R China
3.Hubei Hongshan Lab, Wuhan 430070, Peoples R China
4.Huazhong Agr Univ, Coll Plant Sci & Technol, MOA Key Lab Crop Ecophysiol & Farming Syst Middle, Wuhan 430070, Peoples R China
5.Huazhong Agr Univ, Shenzhen Inst Nutr & Hlth, Wuhan 430070, Peoples R China
6.Chinese Acad Agr Sci, Guangdong Lab Lingnan Modern Agr, Genome Anal Lab, Minist Agr,Agr Genom Inst Shenzhen,Shenzhen Branch, Shenzhen 518120, Peoples R China
7.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Nephrol, Wuhan 430030, Peoples R China
8.Huazhong Agr Univ, Coll Chem, Wuhan 430070, Peoples R China
9.Hainan Univ, Sanya Inst Breeding & Multiplicat, Sch Breeding & Multiplicat, Sanya 572000, Peoples R China
关键词： acute kidney injury; carbon dots; cisplatin; ferroptosis; selenium
期刊名称：ADVANCED SCIENCE （ 影响因子：15.1； 五年影响因子：16.7 ）
ISSN：
年卷期： 2024 年
页码：
收录情况： SCI
摘要： Cisplatin-associated acute kidney injury (AKI) is a severe clinical syndrome that significantly restricts the chemotherapeutic application of cisplatin in cancer patients. Ferroptosis, a newly characterized programmed cell death driven by the lethal accumulation of lipid peroxidation, is widely reported to be involved in the pathogenesis of cisplatin-associated AKI. Targeted inhibition of ferroptosis holds great promise for developing novel therapeutics to alleviate AKI. Unfortunately, current ferroptosis inhibitors possess low bioavailability or perform non-specific accumulation in the body, making them inefficient in alleviating cisplatin-associated AKI or inadvertently reducing the anti-tumor efficacy of cisplatin, thus not suitable for clinical application. In this study, a novel selenium nanomaterial, polyacrylic acid-coated selenium-doped carbon dots (SeCD), is rationally developed. SeCD exhibits high biocompatibility and specifically accumulates in the kidney. Administration of SeCD effectively scavenges broad-spectrum reactive oxygen species and significantly facilitates GPX4 expression by releasing selenium, resulting in strong mitigation of ferroptosis in renal tubular epithelial cells and substantial alleviation of cisplatin-associated AKI, without compromising the chemotherapeutic efficacy of cisplatin. This study highlights a novel and promising therapeutic approach for the clinical prevention of AKI in cancer patients undergoing cisplatin chemotherapy. Intravenously injected SeCD mainly accumulates in the kidney, where SeCD directly scavenges ROS and preserves mitochondrial integrity during the cisplatin challenge. Furthermore, SeCD releases selenium to facilitate GPX4 expression when encountering ROS under cisplatin exposure. Through these mechanisms, SeCD counteracts ferroptosis and alleviates cisplatin-associated AKI, without compromising the anti-tumor efficacy of cisplatin. image
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