Novel Methods for Nitroreductase Detection in Hypoxic Tumor Cells

Hypoxia, a lack of adequate oxygen supply in the body, is a common factor in various diseases and plays a crucial role in cancer cells.1,2 In order to measure and quantify the level of hypoxia within tumor cells, nitroreductase (NTR) is typically monitored due to its overexpression in hypoxic tumors.1,2 Within the past six months, two novel approaches for NTR detection and quantification have been developed. One method utilized fluorescein analogue probes (FBN 1-3) to monitor hypoxic levels in tumor cells.1 Only one probe (FBN-1) was able to perform a reduction in O2 concentration to yield proficient selectivity and sensitivity for hypoxia detection.1 However, subsequent NTR tests showed that a link between NTR concentration and the level of hypoxia may not be present.1 A secondary study synthesized a cationic conjugated polymer (PBFBT-NP) that contained a p-nitrophenyl group in its side chain that acts as a fluorescent probe when in the presence of NTR.2 This new method has a low detection limit of 2.9ng/mL and also allows for fluorescent bioimaging of hypoxic tumor cells.2 Both techniques take a different and unique approach to determining the extent of hypoxia within tumor cells by quantifying the amount of present NTR; however, both groups came to differing conclusions on the impact NTR has on the extent of hypoxia.

1. Luo, S.; Zou, R.; Wu, J.; Landry, M. “A Probe for the Detection of Hypoxic Cancer Cells.” ACS Sensors. 2017. 2. 1139-1145.
2. Zhang, X.; Zhao, Q.; Li, Y.; Duan, X.; Tang, Y. “Multifunctional Probe Based on Cationic Conjugated Polymers for Nitroreductase-Related Analysis: Sensing, Hypoxia Diagnosis, and Imaging.” Analytical Chemistry. 2017. 89. 5503-5510.