Near-Infrared Fluorescent Probe Activated by Nitroreductase for In Vitro and In Vivo Hypoxic Tumor Detection

Research Summary

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. This probe contains folate as a cancer cell targeting moiety and nitro-benzyl as a hypoxia-sensitive fluorophore release trigger. Probe fol-BODIPY was found to provide a rapid fluorescence ‘off-on’ response to hypoxia that is roughly 20-fold greater than that seen in the case of two control probes, which lack the folate and nitro-benzyl moieties, respectively.

In vitro confocal microscopy and flow cytometry analyses, as well as in vivo near-infrared (NIR) optical imaging of CT26 solid tumor-bearing mice, provided support for the contention that fol-BODIPY is more readily taken up by folate receptor-positive CT26 cancer cells and provides a superior fluorescence ‘off-on’ signal under hypoxic conditions than the control probes.

Based on the findings of this study, we propose that fol-BODIPY may have a role to play as a tumor-targeting, hypoxia-activatable probe that allows for direct cancer monitoring both in vitro and in vivo.

Expected Outcomes

This tumor-targeting ability and the observation of specific activation in hypoxic tumor regions leads us to suggest that fol-BODIPY is a promising fluorescence ‘off-on’ probe that could be used in potential applications, such as initial diagnosis of surgery, where the fluorescence-guided image detection of tumor tissue would be beneficial.

Related Figures

• [Figure 1] Near-infrared fluorescent probe activated by nitroreductase for in vitro and in vivo hypoxia tumor detection
• [Figure 2] In vivo tumor detection by means of fluorescence imaging with fol-BODIPY