Liu Shi-Yu, Yan Ai-Min, Guo Wu Ying-Zheng, Fang Yuan-Yuan, Dong Qing-Jian, Li Rong-Rong, Ni Sheng-Nan, Sun Yao, Yang Wen-Chao, Yang Guang-Fu
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, and Chemical Biology Center, College of Chemistry, Central China Normal University, Wuhan 430079, P.R. China.
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, P.R. China.
ACS Nano. 2020 Apr 28;14(4):4244-4254. doi: 10.1021/acsnano.9b09493. Epub 2020 Mar 30.
There is an increasing demand for effective noninvasive diagnosis against common pulmonary diseases, which are rising sharply due to the serious air pollution. Human neutrophil elastase (HNE), a typical protease highly involved in pulmonary inflammatory diseases and lung cancer, is a potential predictor for disease progression. Currently, few of the HNE-targeting probes are applicable due to the limitation in sensitivity and biocompatibility. Herein, we reported the achievement of detection and imaging of HNE by incorporating the HNE-specific peptide substrate, quantum dots (QDs), and organic dyes into the fluorescence resonance energy transfer (FRET) system. The refined nanoprobe, termed , could specifically measure the HNE with excellent sensitivity of 7.15 pM in aqueous solution and successfully image the endogenous and exogenous HNE in living cells. In addition, this nanoprobe enabled HNE imaging in mouse models of lung cancer and acute lung injury, and the HNE activity at high temporal and spatial resolution was continuously monitored. Most importantly, successfully discriminated the serums of patients with lung diseases from those of the healthy controls based on the HNE activity determination. Overall, this study demonstrates the advantages of a FRET-system-based nanoprobe in imaging performance and provides an applicable tool for HNE detection and pulmonary disease diagnosis.
对于针对常见肺部疾病的有效非侵入性诊断的需求日益增加,由于严重的空气污染,这些疾病的发病率正在急剧上升。人中性粒细胞弹性蛋白酶(HNE)是一种典型的蛋白酶,高度参与肺部炎症性疾病和肺癌,是疾病进展的潜在预测指标。目前,由于灵敏度和生物相容性的限制,很少有针对HNE的探针适用。在此,我们报道了通过将HNE特异性肽底物、量子点(QDs)和有机染料纳入荧光共振能量转移(FRET)系统来实现对HNE的检测和成像。这种精制的纳米探针,称为 ,能够在水溶液中以7.15 pM的优异灵敏度特异性地测量HNE,并成功地对活细胞中的内源性和外源性HNE进行成像。此外,这种纳米探针能够在肺癌和急性肺损伤小鼠模型中进行HNE成像,并以高时空分辨率连续监测HNE活性。最重要的是,基于HNE活性测定, 成功地区分了肺病患者和健康对照者的血清。总体而言,本研究证明了基于FRET系统的纳米探针在成像性能方面的优势,并为HNE检测和肺病诊断提供了一种适用的工具。