Construction of ROS-generation system based on lipid droplet-targeting photosensitizer to mediate multiple subcellular organelle damage

Lipid droplets (LDs) have attracted much attention due to their unique structure and key connections with various organelles in cells. Here, we constructed a reactive oxygen species (ROS) -generating system by carefully designing photosensitizers (TT2CN) with proper lipophilicity, excellent light stability and cell imaging ability. In detail, TT2CN can selectively accumulate into LDs (as carriers for TT2CN) and then a subcellular photo-inducible ROS-generating system was formed. Confocal fluorescence imaging revealed the contact behavior of dynamic LDs with other organelles in the cells and the photo-produced ROS can induce multiple organelle damages. Flow cytometry, AM / PI and 3D multicellular tumor spheres (3D MCTs) experiments further verified and demonstrated its promising biological application. This work not only uncovers the communication behavior between LDs and other organelles, but also provides a new anticancer strategy of LDs-mediated photodynamic therapy.