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, –NO 2 , 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.