Human Neutrophil Elastase Activated Fluorescent Probe for Pulmonary Diseases Based on Fluorescence Resonance Energy Transfer Using CdSe/ZnS Quantum Dots
Human Neutrophil Elastase Activated Fluorescent Probe for Pulmonary Diseases Based on Fluorescence Resonance Energy Transfer Using CdSe/ZnS Quantum Dots
复制标题
基于 CdSe/ZnS 量子点荧光共振能量转移的人中性粒细胞弹性蛋白酶激活肺部疾病荧光探针
DOI：
10.1021/acsnano.9b09493
复制
发表时间：
2020-04-28
期刊：
影响因子：
17.1
通讯作者：
Yang, Guang-Fu
中科院分区：
文献类型：
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作者：
Liu, Shi-Yu;Yan, Ai-Min;Yang, Guang-Fu
由于严重的空气污染，对常见肺部疾病的有效非侵入性诊断的需求越来越大。人中性粒细胞弹性蛋白酶(HNE)是一种典型的与肺部炎症性疾病和肺癌密切相关的蛋白酶，是疾病进展的潜在预测因子。目前，由于灵敏度和生物相容性的限制，很少有HNE靶向探针能够在体内应用。在此，我们报道了通过将HNE特异的多肽底物、量子点和有机染料引入到荧光共振能量转移(FRET)系统中，实现了HNE的体外检测和体内成像。这种名为QDP的精细纳米探针可以在水溶液中以7.15 PM的极高灵敏度特异性地测量HNE，并成功地成像活细胞中的内源性和外源性HNE。此外，这种纳米探针能够在肺癌和急性肺损伤的小鼠模型中进行HNE成像，并持续监测高时间和空间分辨率下的HNE活动。最重要的是，基于HNE活性测定，QDP成功地区分了肺部疾病患者和健康对照组的血清。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，并为体内HNE检测和肺部疾病诊断提供了一种适用的工具。
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 in vivo due to the limitation in sensitivity and biocompatibility. Herein, we reported the achievement of in vitro detection and in vivo 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 QDP, 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, QDP 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 in vivo HNE detection and pulmonary disease diagnosis.