A Renal-Clearable Duplex Optical Reporter for Real-Time Imaging of Contrast-Induced Acute Kidney Injury
A Renal-Clearable Duplex Optical Reporter for Real-Time Imaging of Contrast-Induced Acute Kidney Injury
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DOI：
10.1002/anie.201910137
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发表时间：
2019-10-24
影响因子：
16.6
通讯作者：
Pu, Kanyi
中科院分区：
文献类型：
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作者：
Huang, Jiaguo;Lyu, Yan;Pu, Kanyi
尽管其高发病率和死亡率，造影剂诱导的急性肾损伤（CIAKI）仍然是一个诊断困境，因为它依赖于在体外检测不敏感的晚期血液和尿液生物标志物。我们报告的可激活的双链体报告（ADR）的实时在体内成像CIAKI的合成。ADR具有化学发光和近红外荧光（NIRF）信号通道，可被氧化应激（超氧阴离子，O-2（.-））激活。和溶酶体损伤（N-乙酰基-β-d-氨基葡萄糖苷酶，NAG）。凭借其高肾脏清除效率（注射24小时后80%的注射剂量），ADR检测到O-2的连续上调（.-）在CIAKI过程中，在肾小球滤过率（GFR）和组织损伤显著降低之前，在活体小鼠的肾脏中，ADR的性能优于典型的临床检测方法，可提前至少8小时（NIRF）和长达16小时（化学发光）检测CIAKI。
Despite its high morbidity and mortality, contrast-induced acute kidney injury (CIAKI) remains a diagnostic dilemma because it relies on in vitro detection of insensitive late-stage blood and urinary biomarkers. We report the synthesis of an activatable duplex reporter (ADR) for real-time in vivo imaging of CIAKI. ADR is equipped with chemiluminescence and near-infrared fluorescence (NIRF) signaling channels that can be activated by oxidative stress (superoxide anion, O-2(.-)) and lysosomal damage (N-acetyl-beta-d-glucosaminidase, NAG), respectively. By virtue of its high renal clearance efficiency (80 % injected doses after 24 h injection), ADR detects sequential upregulation of O-2(.-) and NAG in the kidneys of living mice prior to a significant decrease in glomerular filtration rate (GFR) and tissue damage in the course of CIAKI. ADR outperforms the typical clinical assays and detects CIAKI at least 8 h (NIRF) and up to 16 h (chemiluminescence) earlier.