Passively-targeted mitochondrial tungsten-based nanodots for efficient acute kidney injury treatment  

作　　者：Qiong Huang Yuqi Yang Tianjiao Zhao Qiaohui Chen Min Liu Shuting Ji Yan Zhu Yunrong Yang Jinping Zhang Haixin Zhao Yayun Nan Kelong Ai 

机构地区：[1]Department of Pharmacy,Xiangya Hospital,Central South University,Changsha,410008,China [2]National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha,410008,China [3]Xiangya School of Pharmaceutical Sciences,Central South University,Changsha,410078,China [4]Hunan Provincial Key Laboratory of Cardiovascular Research,Xiangya School of Pharmaceutical Sciences,Central South University,Changsha,410078,China [5]Geriatric Medical Center,People’s Hospital of Ningxia Hui Autonomous Region,Yinchuan,750002,China

出　　处：《Bioactive Materials》2023年第3期381-393,共13页生物活性材料（英文）

基　　金：National Natural Science Foundation of China(No.81974508,21974134);Hunan Science Fund for Distinguished Young Scholar of China(No.2021JJ10067);Innovation-Driven Project of Central South University(No.202045005);Hunan Provincial Natural Science Foundation of China(No.2021JJ31066);Key Research Project of Ningxia Hui Autonomous Region in 2021 of China(Major Project)(No.2021BEG01001);Key Program of Ningxia Hui Autonomous Region Natural Science Foundation of China(No.2022JJ21059).

摘　　要：Acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in mortality.The burst of reactive oxygen species(ROS)plays a key role in the pathological progression of AKI.Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI.Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases.However,most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules,the main damage site of AKI.Here,an ultra-small Tungsten-based nanodots(TWNDs)with strong ROS scavenging can be very effective for treatment of AKI.TWNDs can reach the tubular site after crossing the glomerular barrier,and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies.To our knowledge,this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI.Through in-depth study of the therapeutic mechanism,such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing mitophagy.In addition,TWNDs can also reduce the infiltration of inflammatory cells.This work provides a new way to passively target mitochondria for AKI,and give inspiration for the treatment of many major diseases closely related to mitochondria,such as myocardial infarction and cerebral infarction.

关 键 词：ROS-scavenging Anti-inflammatory Acute kidney injury Passively-targeted mitochondrial Tungsten-Based Nanodots 

分 类 号：R692[医药卫生—泌尿科学]