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A Probe for the Detection of Hypoxic Cancer Cells
ACS Sensors ( IF 8.2 ) Pub Date : 2017-08-08 00:00:00 , DOI: 10.1021/acssensors.7b00171 Shenzheng Luo 1 , Rongfeng Zou 2 , Junchen Wu 1 , Markita P. Landry
ACS Sensors ( IF 8.2 ) Pub Date : 2017-08-08 00:00:00 , DOI: 10.1021/acssensors.7b00171 Shenzheng Luo 1 , Rongfeng Zou 2 , Junchen Wu 1 , Markita P. Landry
Affiliation
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Hypoxia is a common feature of tumor cells. Nitroreductase (NTR), a common biomarker of hypoxia, has been widely used to evaluate the extent of tumor hypoxia. In this study, three fluorescent probes (FBN-1–3) were synthesized to monitor the extent of hypoxia in cancer cells in real time. FBN-1–3 were composed of a fluorescein analogue and one of three different aromatic nitro groups. Of these probes, FBN-1 showed excellent sensitivity and selectivity in detecting hypoxia via a reduction in O2 concentration. Confocal fluorescence imaging and flow cytometry demonstrated that HepG-2, A549, and SKOV-3 cells incubated with FBN-1 under reduced oxygen conditions showed significantly enhanced fluorescence. A mouse HepG-2 tumor model confirmed that FBN-1 responds rapidly to NTR and can be used to evaluate the degree of tumor hypoxia. The changes in intra- and extracellular NTR in tumor cells were also concurrently monitored, which did not reveal a link between NTR concentration and degree of hypoxia. Our work provides a functional probe for tumor hypoxia, and our results suggest the fluorescent response of our probe is due to a decrease in O2 concentration, and not NTR concentration.
中文翻译：
缺氧癌细胞检测探针
缺氧是肿瘤细胞的共同特征。缺氧的常见生物标志物硝基还原酶（NTR）已被广泛用于评估肿瘤缺氧的程度。在这项研究中，合成了三种荧光探针（FBN-1–3）来实时监测癌细胞中的缺氧程度。FBN-1–3由荧光素类似物和三个不同的芳香族硝基之一组成。在这些探针中，FBN-1在通过减少O 2来检测缺氧方面表现出出色的灵敏度和选择性专注。共聚焦荧光成像和流式细胞术表明，在氧气减少的条件下与FBN-1孵育的HepG-2，A549和SKOV-3细胞显示出显着增强的荧光。小鼠HepG-2肿瘤模型证实FBN-1对NTR响应迅速，可用于评估肿瘤缺氧的程度。还同时监测了肿瘤细胞内和细胞外NTR的变化，但并未揭示NTR浓度与缺氧程度之间的联系。我们的工作为肿瘤缺氧提供了功能性探针，我们的结果表明我们探针的荧光反应是由于O 2浓度的降低而不是NTR浓度的降低。
更新日期：2017-08-08
中文翻译：
缺氧癌细胞检测探针
缺氧是肿瘤细胞的共同特征。缺氧的常见生物标志物硝基还原酶（NTR）已被广泛用于评估肿瘤缺氧的程度。在这项研究中，合成了三种荧光探针（FBN-1–3）来实时监测癌细胞中的缺氧程度。FBN-1–3由荧光素类似物和三个不同的芳香族硝基之一组成。在这些探针中，FBN-1在通过减少O 2来检测缺氧方面表现出出色的灵敏度和选择性专注。共聚焦荧光成像和流式细胞术表明，在氧气减少的条件下与FBN-1孵育的HepG-2，A549和SKOV-3细胞显示出显着增强的荧光。小鼠HepG-2肿瘤模型证实FBN-1对NTR响应迅速，可用于评估肿瘤缺氧的程度。还同时监测了肿瘤细胞内和细胞外NTR的变化，但并未揭示NTR浓度与缺氧程度之间的联系。我们的工作为肿瘤缺氧提供了功能性探针，我们的结果表明我们探针的荧光反应是由于O 2浓度的降低而不是NTR浓度的降低。
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