Synthetic materials with redox-triggers for imaging and drug delivery

Synthetic materials embedded with stimuli-responsive cleavable bonds have been extensively utilized for the development of site-targeted drug delivery system and selective imaging reporters. We developed stimuli-sensitive materials with two different redox switches including trimethyl-locked quinone propionic acid and nitrobenzyl moieties. Novel redox-sensitive polymeric nanoparticles and micelles were prepared from a synthesized monomer containing trimethyl-locked quinone propionic acid as a redox trigger. A hydrophobic cancer drug, paclitaxel, was incorporated into the redox-responsive polymeric nanoparticles and micelles prepared from the synthesize polymers. The effect of redox stress on the nanoparticles and micelles was evaluated with a chemical reductant, sodium dithionite demonstrating that the significant amount of paclitaxel was released at a simulated redox-state compared to the control. Cell viability studies revealed that the polymer was non-toxic and the nanoparticles and micelles could release paclitaxel to suppress breast cancer cell growth. In addition to the drug delivery system, a p-nitrobenzyl moiety redox trigger was utilized to develop a novel NIR fluorescent probe, p-nitrobenzyl 3,7-bis(dimethylamino)-10H-phenothiazine-10-carboxylate for the selective imaging and therapy. Conjugating methylene blue with a p-nitrobenzyl moiety enables it to quench electron transfer within the molecules. Moreover the redox trigger caged probe released active methylene blue by nitroreductase-mediated 1,6-elimination resulting exhibition of strong fluorescence (lambdamax = 680 nm) with the excitation at 580 nm. The fluorescence emission was also induced by incubation with live Escherichia coli bacteria. It was demonstrated that the NIR fluorescent probe generated singlet oxygen after nitroreductase mediated reduction with a laser irradiation at a wavelength of 634 nm. The redox trigger caged NIR fluorescent probe would be a suitable imaging sensor to detect bacteria expressing NTR. In addition, the probe also possesses potential as an MB prodrug which can be applied for the treatment of various diseases.