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Conjugated Oligomer-Based Ultrasensitive Fluorescent Biosensor for Activatable Imaging of Endogenous NQO1 with High Catalytic Efficiency in Cancer Cells
Sensors and Actuators B: Chemical ( IF 8.4 ) Pub Date : 2020-03-12 , DOI: 10.1016/j.snb.2020.127981
Qian Feng , Ziqi Zhang , Qiong Yuan , Min Yang , Chen Zhang , Yanli Tang

Human NAD(P)H: Quinone oxidoreductase 1 (NQO1) is over-expressed in many cancer cells. Thus, it is significant to establish a selective and sensitive method with high signal-to-background ratio for NQO1 detection and cancer diagnosis. Herein, an activatable biosensor based on water-soluble conjugated oligomer (OPFV-TLQ) was designed for highly sensitive detection of NQO1 and visualization imaging of cancer cells. Oligo (ethylene glycol) and the trimethyl lock quinone propionic acid group were modified on the side chain of OPFV-TLQ, which makes the probe possess good water-solubility and low fluorescence background signal, respectively. Interestingly, the benzoquinone can be reduced to hydroquinone by NQO1, which dramatically activates the fluorescence of OPFV-TLQ. Importantly, about 141-fold enhancement in intensity was obtained, which provides one of the highest signal-to-background ratio and the lowest detection limit of 0.068 ng/mL. Additionally, the catalytic constant was 67.71 μM-1 s-1 that is significantly higher than those of other probes, indicating the excellent catalytic efficiency of NQO1. Molecular docking simulation certifies that the probe is an excellent substrate of NQO1. Furthermore, the probe displays high selectivity and biocompatibility, and also has high-fidelity fluorescent signals in NQO1-positive cells. Thus, the biosensor holds great promise in biological applications of cancer cells/tissues imaging and cancer differentiation.



中文翻译:

基于共轭低聚物的超灵敏荧光生物传感器可活化成像的内源性NQO1在癌细胞中具有高催化效率

人NAD(P)H:醌氧化还原酶1(NQO1)在许多癌细胞中过表达。因此,建立一种具有高信噪比的选择性和灵敏方法用于NQO1检测和癌症诊断具有重要意义。在本文中,基于水溶性共轭低聚物(OPFV-TLQ)的可激活生物传感器被设计用于NQO1的高灵敏度检测和癌细胞的可视化成像。在OPFV-TLQ的侧链上修饰了寡聚乙二醇和三甲基锁醌丙酸基团,使该探针分别具有良好的水溶性和低荧光背景信号。有趣的是,NQO1可以将苯醌还原为对苯二酚,从而显着激活OPFV-TLQ的荧光。重要的是,强度提高了约141倍,它提供了最高的信噪比和最低的检测限0.068 ng / mL之一。另外,催化常数为67.71μM-1 s -1显着高于其他探针,表明NQO1具有出色的催化效率。分子对接模拟证明该探针是NQO1的优良底物。此外,该探针显示出高选择性和生物相容性,并且在NQO1阳性细胞中也具有高保真荧光信号。因此,该生物传感器在癌细胞/组织成像和癌症分化的生物学应用中具有广阔的前景。

更新日期:2020-03-12
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