Quaternary ammonium-modified water-soluble boron-dipyrromethene photosensitizers for fluorescence imaging and photodynamic therapy

Abstract

Quaternary-ammonium-functionalized BODIPY photosensitizers were synthesized and systematically investigated to elucidate the influence of meso-phenyl electronic substitution on photophysical properties, intracellular behavior, and photodynamic therapy (PDT) performance. Four water-soluble, cationic BODIPY derivatives bearing para-substituents (–H, –OMe, –NO₂, and –I) were prepared via an azide–alkyne click reaction, enabling a controlled structure–property comparison using a fixed mitochondrial-targeting scaffold. All compounds exhibited characteristic BODIPY absorption and emission profiles, with BHTP, BMTP, and BITP maintaining high fluorescence quantum yields, whereas BNTP showed pronounced fluorescence quenching due to photo-induced electron transfer. Singlet oxygen quantum yields (ΦΔ = 0.01–0.06) were strongly dependent on meso-phenyl electronic effects, with BITP displaying the highest ΦΔ as a result of the heavy-atom effect. Cellular studies revealed negligible dark cytotoxicity for all derivatives and pronounced light-induced cytotoxicity for BITP and BMTP. Confocal co-localization experiments confirmed preferential mitochondrial accumulation, as evidenced by strong overlap with MitoTracker Red signals. Collectively, these results demonstrate that meso-phenyl electronic tuning, combined with a fixed cationic and water-soluble BODIPY scaffold, provides an effective strategy for balancing fluorescence imaging and PDT activity, offering design guidelines for mitochondria-targeted theranostic photosensitizers.