Heavy-Atom Free Bodipy-Borafluorene Photosensitizer Decorated with Coumarin Antenna Selectively Staining Endoplasmic Reticulum for Application in PDT.

The organelle-localized photodynamic therapy (PDT) has become a promising strategy for efficient cancer treatment. The photogeneration of reactive oxygen species in the endoplasmic reticulum (ER) leads to lipid oxidation and causes cell apoptosis or necrosis. However, most of the commercially available ER-localized phototherapeutic agents exhibit dark cytotoxicity related to the presence of heavy atoms. In this contribution, we developed a novel heavy-atom free BODIPY photosensitizer that localizes selectively in the ER with good biocompatibility, small dark cytotoxicity and efficient singlet oxygen generation, causing cellular death in a PDT experiment. The molecular design of the BODIPY PS involves two key elements: (i) replacing of the common BF2 group with the 9-borafluorene which strongly enhances intersystem crossing to the triplet state responsible for photogeneration of singlet oxygen, and (ii) introduction of the pendant coumarin group ensuring ER-localization and serving as light-harvesting antenna for energy transfer to BODIPY core structure. The localization of BODIPY-based PS was confirmed by laser scanning confocal microscopy (LSCM) imaging, and co-staining revealed strong localization within the ER.