Small Molecule Fluorescent Probes for Sensing and Bioimaging of Nitroreductase

Abstract

Hypoxia is a condition caused by a decrease in oxygen and is often seen in cases of cardiac ischemia, solid tumors, inflammation, and other diseases. Tumor hypoxia can result in cancer invasion, metastasis, decreased apoptosis, and resistance to various therapies (chemotherapy, immunotherapy, and radiotherapy), ultimately reducing overall survival rates. These effects of hypoxia underline the need to monitor hypoxia‐associated specific markers for more effective therapeutic intervention. Nitroreductase (NTR) is a common biomarker of hypoxia, via its reduction activity with nitroaromatic compounds to corresponding amino derivatives using NADH and NADPH as cofactor. The NTR expression level can be correlated to cellular hypoxia. Therefore, developing a diagnostic tool for measuring NTR activity is of immense importance for improving treatment efficacies. To leverage NTR activity as a proxy of hypoxia, small molecule based fluorescent probes have been developed as quantifiable probes. To date, several NTR‐sensitive fluorescent probes have been reported. This review is focuses on the advances in these fluorescent NTR probes over the last five years.

Ratiometric near-infrared fluorescent probe for nitroreductase activity enables 3D imaging of hypoxic cells within intact tumor spheroids

“…5,6 In recent years, a large amount of research on hypoxia imaging has focused on bioresponsive fluorescent molecular probes that report nitroreductase (NTR) activity. 7–9 There are two related goals for this ongoing work; one is to develop new research tools to study the biology of hypoxic cells, 1,2 and a more applied goal is to develop hypoxia imaging methods for clinical translation. 10,11…”

A fluorescent probe for imaging nitroreductase with signal amplification in high-viscosity environments

“…10,11 Several methods have been developed to detect NTR, including colorimetric methods, 12 magnetic resonance imaging (MRI), 13 positron emission tomography (PET), 14 fluorescence spectroscopy, etc. 15 Among them, fluorescence spectroscopy has been widely used because of its unique advantages. 9,16,17 Small molecule fluorescent probes that have been developed for the detection of NTR are usually based on a single factor.…”

“…That is, a nitroaromatic compound was introduced as a recognition group, and in the presence of NTR the nitro group was reduced to an amino or hydroxylamine and released a fluorophore, thus enabling the monitoring of NTR. 15,16 However, such single-factorbased probes are often prone to interference and may sometimes face drawbacks such as weak fluorescent signals and low sensitivity, which are not conducive to imaging NTR in cancer cells. In addition to hypoxia, increased viscosity is an important characteristic of cancer cells.…”

Diagnosis of Bacterial Plant Diseases via a Nitroreductase-Activated Fluorescent Sensor

“…Notably, NTR is highly expressed in many bacteria and thus is regarded as a significant biomarker for bacterial detection. Recently, the probes of NTR were widely used for the detection of hypoxia in tumor cells or bacteria, but few of them were applied to detect plant diseases. , Herein, a new NTR-targeted fluorescent sensor, named RNP , was designed and applied for the detection and quantification of plant diseases in vivo (Scheme ). This sensor carrying positive charge could specifically target the negative surface of bacteria and then is expected to be activated by NTR with ultrahigh catalytic efficiency ( k cat / K m = 29.16 μM –1 ·min –1 ) to produce the strong fluorescence.…”

“…Recently, the probes of NTR were widely used for the detection of hypoxia in tumor cells or bacteria, but few of them were applied to detect plant diseases. 20,21 Herein, a new NTR-targeted fluorescent sensor, named RNP, was designed and applied for the detection and quantification of plant diseases in vivo (Scheme 1). This sensor carrying positive charge could specifically target the negative surface of bacteria 22 Instrumentation.…”