A Probe for the Detection of Hypoxic Cancer Cells

• Published in: ACS sensors Vol. 2; no. 8; pp. 1139 - 1145
• Main Authors: Luo, Shenzheng, Zou, Rongfeng, Wu, Junchen, Landry, Markita P
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25-08-2017
• Subjects: fluorescent probes; hypoxia sensors; hypoxic fluorescent imaging; nitroreductase; tumor detection; nitroreductase; tumor detection; hypoxia sensors; fluorescent probes; hypoxic fluorescent imaging
• ISSN: 2379-3694; 2379-3694
• DOI: 10.1021/acssensors.7b00171

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.