Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury

            分子光学成像探针的早期诊断药物引起的急性肾损伤

主讲人：唐丹丹

Nature Materials (IF 41.2) Pub Date : 2019-05-27 ,DOI:10.1038/s41563-019-0378-4

Abstract:

      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.

摘要：

          具有高发病率和死亡率的药物性急性肾损伤（AKI）在医院中诊断不佳，并且在药物发现中缺乏评估。在这里，我们报告了具有高肾清除效率的分子肾探针（MRP）的开发，用于药物诱导的AKI的体内光学成像。MRPs特异性地激活其近红外荧光或化学发光信号，朝向AKI的前驱生物标志物，包括超氧阴离子，N-乙酰基-Β-D-葡萄糖胺酶和半胱天冬酶-3，从而可以对活小鼠肾脏中的多个分子事件进行纵向成像。重要的是，它们原位报告了氧化应激，溶酶体损伤和细胞凋亡的顺序发生，这在AKI（肾小球滤过减少）的临床表现之前。这种主动成像机制允许MRPs比现有成像方法至少提前36小时无创地检测顺铂诱导的AKI的发作。MRP 还可以作为光学尿液分析的外源性示踪剂，优于典型的临床/临床前测定，证明了其在 AKI 早期诊断方面的临床前景。