Hydrazone-based Photocages: A Novel Class for Precise Sub-Organelle Visualization and Cargo Release

Photocages are widely investigated for their potential in bioimaging, controlled drug release, and the modulation of cellular processes. Novel universal photoreactive groups (PRGs) can significantly expand the structural diversity of photocages. In this work, we developed a novel class of PRGs based on the classic aldehyde-hydrazone moiety by conjugating several fluorescent aldehydes with various substituted phenylhydrazines. The resulting aldehyde-hydrazone photocages, including five series of new photocages PC, TP, CM, BW and FY, underwent controlled degradation upon exposure to specific light wavelengths of 365-450 nm, releasing corresponding fluorescent aldehydes of pyrene, anthracene, perylene, cinnamaldehyde, and tetraphenylethylene (TPE). Their fluorescent enhancements, redshifts or blueshifts in fluorescence spectra were clearly observed. To further demonstrate the light-controlled feasibility of the synthesized photocages in the field of molecule release and sub-organelle targeting, morpholine-hydrazone based hybrid BW3MP was constructed for sub-organelle lysosome-specific imaging and cargo release of cargo unit MP. The photo-induced cleavage of the C=N bond, visualized in real time through fluorescence change during confocal imaging, demonstrates a high release efficiency of MP (75.5%, BW3MP). Taken together, our work holds significant promise for the advancement of novel drug delivery systems (DDSs).