Tumor
hypoxia is correlated with increased resistance to chemotherapy
and poor overall prognoses across a number of cancer types. We present
here a cancer cell-selective and hypoxia-responsive probe (fol-BODIPY) designed on the basis of density functional theory (DFT)-optimized
quantum chemical calculations. The fol-BODIPY probe was
found to provide a rapid fluorescence “off–on”
response to hypoxia relative to controls, which lack the folate or
nitro-benzyl moieties. In vitro confocal microscopy
and flow cytometry analyses, as well as in vivo near-infrared
optical imaging of CT26 solid tumor-bearing mice, provided support
for the contention that fol-BODIPY is more readily accepted
by folate receptor-positive CT26 cancer cells and provides a superior
fluorescence “off–on” signal under hypoxic conditions
than the controls. Based on the findings of this study, we propose
that fol-BODIPY may serve as a tumor-targeting, hypoxia-activatable
probe that allows for direct cancer monitoring both in vitro and in vivo.