Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury
Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury
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DOI：
10.1038/s41563-019-0378-4
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发表时间：
2019-10-01
期刊：
影响因子：
41.2
通讯作者：
Pu, Kanyi
中科院分区：
文献类型：
--
作者：
Huang, Jiaguo;Li, Jingchao;Pu, Kanyi
药物性急性肾损伤（阿基）是一种发病率和死亡率较高的疾病，目前医院对它的诊断和药物研发评价不足。在这里，我们报告了具有高肾脏清除效率的分子肾脏探针（MRP）的开发，用于药物诱导的阿基的体内光学成像。MRP特异性地激活其近红外荧光或化学发光信号，这些信号针对阿基的前驱生物标志物，包括超氧阴离子、N-乙酰基-β-D-氨基葡萄糖苷酶和半胱天冬酶-3，从而实现活体小鼠肾脏中多个分子事件的纵向成像的示例。重要的是，他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，这先于阿基的临床表现（肾小球滤过降低）。这种主动成像机制允许MRPs非侵入性地检测顺铂诱导的阿基的发作，比现有的成像方法早至少36小时。MRP还可以作为光学尿液分析的外源性示踪剂，其性能优于典型的临床/临床前测定，证明了其用于早期诊断阿基的临床前景。
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-beta-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.