Naphthalimides in fluorescent imaging of tumor hypoxia – An up-to-date review

Hypoxia is a distinctive characteristic of advanced solid malignancies that results from a disparity between oxygen supply and its consumption. The degree of hypoxia is believed to have adverse prognostic significance. Therefore detecting cellular hypoxia can potentially offer insights into the grade of tumour as well as its evolution towards a progressive malignant phenotype, which clinically translates to greater metastatic potential and treatment resistance. Fluorescence imaging to visualize hypoxia in biological systems is a minimally-invasive method. Recently there are several reports on interdisciplinary research that aims at developing functional probes that can be efficiently used for non-invasive imaging of hypoxic tumours. Upregulated levels of nitroreductase (NTR) is detected in hypoxic solid malignancies, and this characteristic feature is increasingly utilized in the development of NTR-targeted fluorescent molecules to selectively sense hypoxia in vivo. The present review summarizes various reports published on the design concepts of nitro naphthalimide-based bio-reductive fluorescent sensors that can be applied noninvasively to image hypoxia in cancer.