Evaluation of GSH-generating prodrug via sulfonamide-induced “integrative” platform for selective cancer therapy
A sulfonamide-appended gemcitabine prodrug was newly reported. The prodrug can efficiently distinguishing GSH from cysteine and homocysteine. Upon reaction with GSH that are relatively abundant in tumor cells, sulfonyl group cleavage occurs as well as active drug GMC release and concomitantly the innate fluorescence intensity increase. As a proof of concept, the colocalization experiments demonstrated that the probe LHX by receptor-mediated endocytosis bestowed significantly improved therapeutic efficacy and low side effects. Thus, these results suggest that the theranostic agent is promising “integrative” platform for efficient cancer therapy, which can be real-time activated that are not only selectively monitored and localized by specific tumour cells, but also undergo cascaded cleavage to induce both a fluorogenic response and release an active cytotoxic drug.