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A high-selectivity fluorescent probe for hypoxia imaging in cells and a tumor-bearing mouse model.
Analyst ( IF 3.6 ) Pub Date : 2020-02-03 , DOI: 10.1039/c9an02436k
Yue Wang 1 , Xiaoyue Han , Xia Zhang , Li Zhang , Lingxin Chen
Affiliation  

Nitroreductase (NTR) with a high expression level in tumors has been considered as a biomarker of highly aggressive hypoxia tumors. Thus, it is important to develop powerful tools for tumor hypoxia detection. Here, we developed a two-photon fluorescent probe hTP-NNO2 for NTR detection. The probe with one-step synthesis exhibited high yield. hTP-NNO2 showed high selectivity and sensitivity for NTR and the detection limit was as low as 43 ng mL-1. hTP-NNO2 also showed low cytotoxicity and high stability, indicating that hTP-NNO2 is suitable for NTR detection in real-time and in situ under physiological conditions. hTP-NNO2 was used for NTR imaging in hypoxia cells and the fluorescence intensity of hTP-NNO2 increased with decreasing oxygen concentration. Benefiting from the advantages of two-photon fluorescent probes, we performed NTR detection in deep brain tissue with an imaging depth of up to 100 μm. hTP-NNO2 was further successfully applied for NTR detection in zebrafish and tumors. These results indicated that we developed a promising fluorescence imaging tool for NTR detection in vitro and in vivo.

中文翻译:

一种高选择性荧光探针,用于细胞内低氧成像和荷瘤小鼠模型。

在肿瘤中具有高表达水平的硝基还原酶(NTR)被认为是高度侵袭性缺氧肿瘤的生物标记。因此,重要的是开发强大的工具来检测肿瘤缺氧。在这里,我们开发了一种用于NTR检测的双光子荧光探针hTP-NNO2。具有一步合成的探针显示出高产率。hTP-NNO2对NTR表现出高选择性和灵敏度,检测限低至43 ng mL-1。hTP-NNO2还显示出低细胞毒性和高稳定性,表明hTP-NNO2适合在生理条件下实时和原位检测NTR。hTP-NNO2用于缺氧细胞的NTR成像,并且hTP-NNO2的荧光强度随着氧气浓度的降低而增加。受益于双光子荧光探针的优势,我们在深部脑组织中进行了NTR检测,成像深度高达100μm。hTP-NNO2进一步成功地用于斑马鱼和肿瘤的NTR检测。这些结果表明,我们开发了一种有前途的荧光成像工具,可用于体内外的NTR检测。
更新日期:2020-02-17
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