A novel BODIPY-based reductant-sensitive near-infrared fluorescent probe for real-time reporting azoreductase-triggered release

Azoreductase-based near-infrared (NIR) fluorescent probe represents a potent tool in the biological detection and drug delivery for treating hypoxic tumor and colon disease. Various azobenzene derivatives have aroused wide attention to develop these fluorescent probes based on the “profluorescence”, however, most of the azobenzene derivatives have absorptions and emissions in the visible region. Herein, a novel NIR fluorescent probe ADP-Azo has been designed and synthesized, which is non-conventional azobenzene derivatives composed of a NIR fluorescent molecule Aza-BODIPY connected directly with azobenzene moiety for a convenient access to quench the fluorescence. In the presence of azoreductase, the azo bonds of ADP-Azo are cleaved and the fluorescence of the probe changes from “OFF” to “ON”. In addition, the drug-loaded nanoprobe are successfully fabricated by self-assembly of the amphiphilic polymer mPEG2k-ADP-Azo derived from the ADP-Azo in PBS buffer solution. These drug-loaded micelles indicate efficiently “ON-OFF” switch of NIR fluorescence accompanied by drug release under the action of azoreductase in a simulated colon environment. The fluorescent nanoprobes based ADP-Azo demonstrate the potential applications in fluorescence imaging and controlled drug release for treating hypoxic tumor and colon disease.