Cationic halogenated BODIPYs as water-soluble photosensitizers for photodynamic therapy

Abstract

This paper reports the synthesis of three water-soluble halogenated boron-dipyrromethene (BODIPY) photosensitizers (BHTM, BBrTM, and BITM) functionalized with cationic groups to improve biological performance. Introduction of bromine and iodine at the 2,6-positions promoted singlet-oxygen generation through the heavy-atom effect, with quantum yields (ϕ_Δ) of 0.59 for BBrTM and 0.91 for BITM, higher than that (0.11) for the non-halogenated analog BHTM. Incorporation of cationic substituents enhanced hydrophilicity, enabling effective dispersion in aqueous environments and facilitating cellular uptake. Biological evaluations in MCF-7 and HeLa cancer cells revealed minimal dark cytotoxicity (>95% viability at 400 nM) but pronounced phototoxicity under 530 nm light irradiation, confirming efficient photodynamic therapy activity. Confocal laser scanning microscopy further demonstrated favorable fluorescence imaging capability and cytoplasmic localization. Collectively, these findings highlight the potential of water-soluble halogenated BODIPY dyes as dual-function agents for fluorescence-imaging-guided photodynamic therapy.