posted on 2017-07-25, 00:00authored byShenzheng Luo, Rongfeng Zou, Junchen Wu, Markita P. Landry
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.