Nitroreductase-triggered activation of a novel caged fluorescent probe obtained from methylene blue

Abstract

A near-infrared fluorescent probe based on methylene blue (p-NBMB) was developed for the detection of nitroreductase. Conjugating methylene blue with a p-nitrobenzyl moiety enables it to be activated by nitroreductase-catalyzed 1,6-elimination, resulting in the release of an active methylene blue fluorophore.

In Vivo Chemiluminescent Imaging Agents for Nitroreductase and Tissue Oxygenation

“…20 Nitroreductase-dependent chemiluminescence was first evaluated in PBS (10 mM, pH 7.4) buffer containing 10% Emerald II Enhancer using an F-7000 Hitachi spectrophotometer. The Emerald II Enhancer is a commercial aqueous solution that contains a proprietary cationic polymer and a dye with optical properties similar to fluorescein, with a peak absorption at 505 nm (Figure S1).…”

“…In recent years, small molecule fluorescence imaging agents have been developed that take advantage of the reduction of azobenzene, nitrobenzene, nitrofuran, and nitroimidazole functional groups to release a caged fluorescent dye. 20 Despite progress towards in vivo hypoxia imaging with near-infrared emitting fluorophores, complications arising from auto-fluorescence, background, and light scattering remain problematic. Bioluminescent substrates for nitroreductase have been developed and have found application for imaging bacterial infection and cancer cells engineered to express bacterial nitroreductase.…”

Targeting a Targeted Drug: An Approach Toward Hypoxia‐Activatable Tyrosine Kinase Inhibitor Prodrugs

“…[7, 8] In addition, more recently, several highly innovative approaches using imaging agents for in vivo biomarker detection, for example, enhanced levels of reductive enzymes, have been published. [9] In the future, these new methods could also be useful for verifying the presence and determining the amount of suitable enzymes for prodrug activation.…”

Trimethyl Lock: A Multifunctional Molecular Tool for Drug Delivery, Cellular Imaging, and Stimuli‐Responsive Materials

“…Principle of metabolic tissue engineering by ManNAz precursor and NQO1-sensitive masked ManNAz precursor. [175][176][177][178][179][180] Furthermore, several bacteria possess nitroreductases and are, therefore, able to degrade nitro compounds; [181] this can also lead to activation of antibacterial drugs such as metronidazole. [174] Nitroreductases are especially overexpressed in hypoxic tissue, such as cancerc ells, and this makes them reliable biomarkers fort he degree of hypoxiai nt umors.…”