Nitroreductase Detection and Imaging with a Biotin-Guided Near-Infrared Fluorescent Probe Exhibiting a Large Stokes Shift in Cells, Animal Tumors, and Sepsis-Induced Acute Lung Injury

IF 8 1区 化学 Q1 CHEMISTRY, ANALYTICAL
Chia-Hsiang Chen, Tzu-Hsiu Lu, Shu-Pao Wu
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Abstract

Quantitative measurement of in vivo hypoxia is crucial for evaluating cancer treatments and diagnostics. We introduce Biotin-XC-NO2, a near-infrared fluorescent probe activated by nitroreductase (NTR), specifically designed to detect NTR activity in hypoxic tumor environments. The probe incorporates a xanthene-based fluorophore with a large Stokes shift and a biotin group to enhance cellular uptake. Upon NTR-mediated reduction of the nitro group, fluorescence increases 50-fold at 640 nm, with a detection limit as low as 0.15 ng/mL. In cellular and animal models, Biotin-XC-NO2 demonstrated high specificity for NTR, enabling real-time imaging in HeLa cells, zebrafish, and tumor-bearing mice. It also identified NTR overexpression in sepsis-induced acute lung injury, highlighting its potential for clinical diagnostics and therapeutic monitoring. Overall, Biotin-XC-NO2 is a promising tool for imaging NTR activity, advancing cancer research and enhancing the understanding of inflammatory diseases.

Abstract Image

用生物素引导的近红外荧光探针检测和成像硝基还原酶,显示细胞、动物肿瘤和败血症诱导的急性肺损伤中的大斯托克斯转移
体内缺氧的定量测量是评估癌症治疗和诊断的关键。我们介绍了一种由硝基还原酶(NTR)激活的近红外荧光探针Biotin-XC-NO2,专门用于检测缺氧肿瘤环境中NTR的活性。该探针结合了具有大斯托克斯位移的基于杂蒽的荧光团和生物素组,以增强细胞摄取。ntr介导的硝基还原后,在640 nm处荧光增强50倍,检出限低至0.15 ng/mL。在细胞和动物模型中,Biotin-XC-NO2显示出对NTR的高特异性,能够在HeLa细胞、斑马鱼和荷瘤小鼠中进行实时成像。该研究还发现了NTR在脓毒症诱导的急性肺损伤中的过表达,突出了其在临床诊断和治疗监测方面的潜力。总的来说,Biotin-XC-NO2是一种很有前途的工具,用于成像NTR活性,推进癌症研究和增强对炎症性疾病的理解。
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来源期刊
Sensors and Actuators B: Chemical
Sensors and Actuators B: Chemical 工程技术-电化学
CiteScore
14.60
自引率
11.90%
发文量
1776
审稿时长
3.2 months
期刊介绍: Sensors & Actuators, B: Chemical is an international journal focused on the research and development of chemical transducers. It covers chemical sensors and biosensors, chemical actuators, and analytical microsystems. The journal is interdisciplinary, aiming to publish original works showcasing substantial advancements beyond the current state of the art in these fields, with practical applicability to solving meaningful analytical problems. Review articles are accepted by invitation from an Editor of the journal.
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