Cheng Penghui, Zeng Ziling, Liu Jing, Liew Si Si, Hu Yuxuan, Xu Mengke, Pu Kanyi
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Nat Biomed Eng. 2025 May;9(5):686-699. doi: 10.1038/s41551-024-01340-1. Epub 2025 Jan 29.
The utility of urinary tests for the monitoring of the treatment efficacy and adverse events of anticancer therapies is constrained by the low concentration of relevant urinary biomarkers. Here we report, using mice with lung cancer and treated with chemotherapy, of a urinary fluorescence test for the concurrent monitoring of the levels of a tumour biomarker (cathepsin B) and of a biomarker of chemotherapy-induced kidney injury (N-acetyl-β-D-glucosaminidase). The test involves two intratracheally administered urinary reporters leveraging caged bioorthogonal click handles for the biomarker-dependent activation of 'clickability' and renal clearance, and the bioorthogonal click reaction of each renally cleared reporter with paired fluorescence indicators in the collected urine. In mouse models of chemotherapy-treated orthotopic lung cancer and of cisplatin-induced kidney injury, lower urinary fluorescence signals (which can be measured by a smartphone camera) for tumour and kidney injury levels positively correlated with animal weight gain and survival time. Biomarker-activated bioorthogonal click reactivity and renal clearance combined with bioorthogonally triggered fluorescence in vitro may enable specific, sensitive and rapid urinary assays for the monitoring of other physiopathological processes.
尿液检测在监测抗癌治疗的疗效和不良事件方面的效用受到相关尿液生物标志物浓度较低的限制。在此，我们报告了一种针对肺癌小鼠并接受化疗的尿液荧光检测方法，用于同时监测肿瘤生物标志物（组织蛋白酶B）和化疗诱导的肾损伤生物标志物（N - 乙酰 - β - D - 氨基葡萄糖苷酶）的水平。该检测涉及两种经气管内给药的尿液报告分子，利用笼形生物正交点击手柄实现生物标志物依赖性的“可点击性”激活和肾脏清除，以及每个经肾脏清除的报告分子与收集尿液中配对荧光指示剂的生物正交点击反应。在化疗治疗的原位肺癌和顺铂诱导的肾损伤小鼠模型中，肿瘤和肾损伤水平的较低尿液荧光信号（可通过智能手机摄像头测量）与动物体重增加和生存时间呈正相关。生物标志物激活的生物正交点击反应性和肾脏清除与体外生物正交触发的荧光相结合，可能实现用于监测其他生理病理过程的特异性、灵敏且快速的尿液检测。
