Mitochondrial targeting of BODIPY photosensitizer with enhanced phototoxicity toward aggressive breast cancer cells compared to non-neoplastic breast epithelial cells

Targeting specific cellular organelles has become an important facet of cancer therapy. Photodynamic therapy (PDT), which spatially targets tumours, may also benefit from photosensitizers capable of localizing within specific cellular organelles. This report details the straightforward synthesis, characterization, photophysical properties, and biological effects of new cationic BODIPY (BDP) dyes capable of specific localization within cellular mitochondria— BDP-mito1 and its iodinated congener BDP-mito2. BDP-mito2 generates singlet oxygen with a quantum yield (ϕ Δ ) of 0.64. In addition to Type II mechanism, we present evidence of production of superoxide radicals (Type I mechanism). Studies under physiological environment show that BDP-mito2 photo-reacts with plasmid DNA when irradiated with low energy light < 550 nm. Cell studies show mitochondrial localization of BDP-mito1 and BDP-mito2 . There was no dark toxicity but dramatic phototoxicity of BDP-mito2 (IC50 230 nM) towards an aggressive breast cancer cell line when irradiated near the PDT window for maximum penetration. Viability loss due to phototoxicity was less pronounced in non-neoplastic breast epithelial cells suggesting greater efficacy within tumour cells. We foresee this report will spur new developments for sub-cellular targeting of cancer cell vulnerabilities in PDT. Mitochondrial targeting of BODIPY photosensitizer with enhanced phototoxicity toward aggressive breast cancer cells compared to non-neoplastic breast epithelial cells.