Azo-based Fluorogenic Probes for Biosensing and Bioimaging: Recent Advances and Upcoming Challenges

Abstract : The use of non-fluorescent azo dyes as dark quenchers in activatable optical bioprobes based on Förster resonance energy transfer (FRET) mechanism and designed to target a wide range of enzymes, has been well established for over two decades. The key value of the azo moiety (-N=N-) to also act as an efficient "ON-OFF" switch of fluorescence once introduced within the core structure of conventional organic-based fluorophores (mainly fluorescent aniline derivatives) has been recently exploited in the developement of alternative reaction-based small-molecule probes based on the "pro-fluorescence" concept. These unprecedented "azobenzene-caged" fluorophores are valuable tools for the detection of a wide range of reactive (bio)analytes. This review highlights the most recent and relevant advances that have been made in the design and biosensing/bioimaging applications of azo-based fluorogenic probes. Emphasis is also placed on relevant achievements in synthesis of bioconjugatable/biocompatible azo dyes used as starting building blocks in the rational and rapid construction of these fluorescent chemodosimeters. Finally, a brief glimpse of the possible future biomedical applications (theranostics) of these "smart" azobenzene-based molecular systems is presented.