Innovative application of conventional hydrazone analogues as photocages with ultrahigh photolysis efficiency for dynamic bioimaging and prodrug construction

In this study, we explore a novel application of conventional hydrazone analogues SA and LG series as a new class of photocages, which are successfully developed by coupling various phenylhydrazines with two aldehydes of coumarin and triphenylamine (TPA) via one-step reaction. Under 450 nm irradiation, these compounds exhibit significant photolysis behavior, achieving impressive conversion rate of up to 99.0 %. Notably, this ultrahigh photolysis efficiency may represent the highest conversion rate reported to date. Meanwhile, we propose the photolysis mechanism identified as a photooxidation process based on the identification of key intermediates and final products. In cellular studies, the uncaging process is real-time visualized in MCF-7 cancer cells, as evidenced by fluorescence intensity increase over irradiation time, demonstrating these hydrazone-based photocage spotential for bioimaging applications. Moreover, by conjugating one of the LG photocage with a staurosporine analog, we develop a photo-controlled drug delivery system (DDS), LG-STS, which also demonstrate efficient photolysis. The staurosporine analog can be released and visualized via a progressive fluorescence enhancement and a 25-fold increase in anticancer activity at cellular level. Overall, our study highlights the significant potential of hydrazone-based photocages for applications in fluorescent bioimaging and photo-controlled drug release, providing a promising platform for advanced DDS development.