Real-Time Monitoring Renal Impairment Due to Drug-Induced AKI and Diabetes-Caused CKD Using an NAG-Activatable NIR-II Nanoprobe
Real-Time Monitoring Renal Impairment Due to Drug-Induced AKI and Diabetes-Caused CKD Using an NAG-Activatable NIR-II Nanoprobe
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DOI：
10.1021/acs.analchem.1c03926
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发表时间：
2021-12-07
影响因子：
7.4
通讯作者：
Gu, Xianfeng
中科院分区：
文献类型：
--
作者：
Tan, Jiahui;Yin, Kai;Gu, Xianfeng
肾功能的实时体内光学成像对于急性肾损伤（AKI）和慢性肾病（CKD）等肾脏疾病的诊断非常重要，这些疾病在全球范围内发病率和死亡率很高。然而，已报道的光学显像剂由于灵敏度低、组织穿透性差、背景干扰显着，在早期识别 AKI 或 CKD 方面仍存在局限性。在此，开发了一种 N-乙酰基-β-D-氨基葡萄糖苷酶 (NAG) 可激活的第二近红外 (NIR-II) 荧光纳米探针 (BOD-II-NAG-NP)，用于监测药物诱导的 AKI 的进展和糖尿病引起的 CKD 的体内成像。 NAG作为肾脏疾病的生物标志物，能够特异性激活BOD-II-NAG-NP释放NIR-II荧光信号，从而实现活体小鼠肾功能障碍的体内成像。重要的是，这种主动成像机制使得 BOD-II-NAG-NP 能够比大多数现有检测方法提前至少 32 小时无创地检测药物诱导的 AKI 的发作，这表明 BOD-II-NAG-NP 有潜力成为 AKI 早期诊断的光学成像剂。此外，BOD-II-NAG-NP产生的NIR-II荧光可以深入穿透糖尿病肾病小鼠相对较厚的脂肪层，并提供高分辨率的体内成像，表明BOD-II-NAG-NP具有精准诊断CKD的临床潜力。
Real-time in vivo optical imaging of kidney function is important for the diagnosis of renal diseases, such as acute kidney injury (AKI) and chronic kidney disease (CKD), with high morbidity and mortality worldwide. However, the reported optical imaging agents still have limitations for identifying AKI or CKD in the early stage due to their low sensitivity, poor tissue penetration, and significant background interference. Herein, an N-acetyl-beta-D-glucosaminidase (NAG)-activatable second near-infrared (NIR-II) fluorescent nanoprobe (BOD-II-NAG-NP) is developed for monitoring the progression of drug-induced AKI and in vivo imaging of diabetes-caused CKD. NAG, as a biomarker of renal diseases, is able to specifically activate BOD-II-NAG-NP to release NIR-II fluorescence signals, enabling in vivo imaging of kidney dysfunctions in living mice. Importantly, such an active imaging mechanism allows BOD-II-NAG-NP to noninvasively detect the onset of drug-induced AKI at least 32 h earlier than the most existing assays, which indicates that BOD-II-NAG-NP has the potential to be an optical imaging agent for the early diagnosis of AKI. Moreover, NIR-II fluorescence produced by BOD-II-NAG-NP could deeply penetrate into the relatively thick layers of fat in diabetic nephropathy mice and provide in vivo imaging with high resolution, indicating that BOD-II-NAG-NP has clinical potential for precision diagnosis of CKD.