Fast Imaging of Mitochondria and Efficient Generation of Singlet Oxygen by Red Fluorescent BODIPY Photosensitizers

Abstract

The biomedical applications of BODIPY fluorophores are limited by challenges such as short-wavelength emission, high hydrophobicity, and poor selectivity. To address these issues, two water-soluble red-emitting BODIPY derivatives, namely, PSPyBDP and I-PSPyBDP, were synthesized by conjugating pyridine units to the BODIPY core, followed by the ring-opening reactions with 1,3-propanesulfonate. Notably, PSPyBDP showed fast mitochondrial imaging capability (∼5 min), indicating its potential as an alternative to mitochondria tracker. I-PSPyBDP, with the heavy-atom effect, could effectively produce singlet oxygen (¹O₂) under irradiation at 660 nm in a short time (∼1 min) with a ¹O₂ quantum yield of 0.89. Cytotoxicity assays revealed that the BODIPY derivatives exhibited phototoxicity to HeLa cells while maintaining low dark toxicity. Interestingly, they had low toxicity against normal COS-7 cells. Confocal imaging and flow cytometry confirmed that the BODIPY derivatives could increase intracellular reactive oxygen species (ROS), reduce mitochondrial membrane potential, and induce apoptosis upon irradiation. These findings suggest their promising application in photodynamic therapy (PDT) for tumors.