School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore.
Nat Mater. 2019 Oct;18(10):1133-1143. doi: 10.1038/s41563-019-0378-4. Epub 2019 May 27.
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.
药物引起的急性肾损伤（AKI）具有高发病率和死亡率，但在医院中诊断不足，在药物发现中评估不足。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，用于药物引起的 AKI 的体内光学成像。MRP 特异性地激活它们的近红外荧光或化学发光信号，针对 AKI 的前导生物标志物，包括超氧阴离子、N-乙酰-β-D-氨基葡萄糖苷酶和半胱天冬酶-3，从而能够对活小鼠肾脏中的多个分子事件进行纵向成像。重要的是，它们原位报告氧化应激、溶酶体损伤和细胞凋亡的顺序发生，这先于 AKI 的临床表现（肾小球滤过率降低）。这种主动成像机制使 MRP 能够非侵入性地检测顺铂引起的 AKI 的发生，比现有的成像方法至少早 36 小时。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/临床前检测，证明了它们在 AKI 的早期诊断中的临床应用前景。
