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Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury.
Nature Materials ( IF 37.2 ) Pub Date : 2019-05-27 , DOI: 10.1038/s41563-019-0378-4
Jiaguo Huang 1 , Jingchao Li 1 , Yan Lyu 1 , Qingqing Miao 1 , Kanyi Pu 1
Affiliation  

Drug-induced acute kidney injury (AKI) with a high morbidity and mortality is poorly diagnosed in hospitals and deficiently evaluated in drug discovery. Here, we report the development of molecular renal probes (MRPs) with high renal clearance efficiency for in vivo optical imaging of drug-induced AKI. MRPs specifically activate their near-infrared fluorescence or chemiluminescence signals towards the prodromal biomarkers of AKI including the superoxide anion, N-acetyl-β-D-glucosaminidase and caspase-3, enabling an example of longitudinal imaging of multiple molecular events in the kidneys of living mice. Importantly, they in situ report the sequential occurrence of oxidative stress, lysosomal damage and cellular apoptosis, which precedes clinical manifestation of AKI (decreased glomerular filtration). Such an active imaging mechanism allows MRPs to non-invasively detect the onset of cisplatin-induced AKI at least 36 h earlier than the existing imaging methods. MRPs can also act as exogenous tracers for optical urinalysis that outperforms typical clinical/preclinical assays, demonstrating their clinical promise for early diagnosis of AKI.

中文翻译:

分子光学成像探针可用于早期诊断药物诱发的急性肾损伤。

具有高发病率和死亡率的药物诱发的急性肾损伤(AKI)在医院中诊断不佳,并且在药物发现中评估不足。在这里,我们报告了具有高肾脏清除效率的分子肾探针(MRP)的发展,用于药物诱导的AKI的体内光学成像。MRP特异性地激活其近红外荧光或化学发光信号至AKI的前体生物标记物,包括超氧阴离子,N-乙酰基-β-D-氨基葡萄糖苷酶和caspase-3,从而可以对肾脏多个分子事件进行纵向成像。活着的老鼠。重要的是,他们原位报道了氧化应激,溶酶体损伤和细胞凋亡的顺序发生,这是在AKI(肾小球滤过减少)的临床表现之前。这种主动的成像机制使MRP能够比现有成像方法至少提前36小时非侵入性地检测顺铂诱导的AKI的发作。MRP还可以作为光学尿液分析的外源示踪剂,其性能优于典型的临床/临床前测定,证明了其对AKI早期诊断的临床前景。
更新日期:2019-05-27
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