Constructing pH-Responsive and Tunable Azo-Phenol-Based o-Nitrobenzyl Photocages.

Multiple triggered-release strategies are widely utilized to control the release of caged target molecules. Among them, photocages with conditional triggers provide extra layers of control in photorelease. In this work, we designed a series of pH-responsive photocages that could be triggered under irradiation and specific intracellular pH values. We conjugated the pH-sensitive phenolic groups with o-nitrobenzyl (oNB) to form azo-phenolic NPX photocages with tunable pKa. Our azo-phenol-based oNB photocages showed differentiable photoreleasing profiles at pH 5.0, 7.2 and 9.0. By attaching fluorogenic cargos, we were able to show that one of the photocages, NPdiCl, could be used to differentiate between acidic pH 5.0 and neutral pH 7.2 in cells under artificial pH conditions. Finally, we demonstrated that NPdiCl is a promising pH-responsive photocage for photoreleasing cargo inside acidic tumor cells.