Near-Infrared Fluorescent Probe Activated by Nitroreductase for In Vitro and In Vivo Hypoxic Tumor Detection.
Sanu KaranMi Young ChoHyunseung LeeHwunjae LeeHye Sun ParkMahesh SundararajanJonathan L SesslerKwan Soo HongPublished in: Journal of medicinal chemistry (2021)
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.
Keyphrases
- living cells
- fluorescent probe
- density functional theory
- single molecule
- molecular dynamics
- endothelial cells
- flow cytometry
- papillary thyroid
- computed tomography
- high resolution
- metabolic syndrome
- squamous cell
- magnetic resonance imaging
- squamous cell carcinoma
- energy transfer
- drug delivery
- dual energy
- adipose tissue
- high fat diet induced
- young adults
- locally advanced
- childhood cancer
- rectal cancer
- fluorescence imaging
- binding protein