Lipophilic quaternary ammonium-functionalized BODIPY photosensitizers for mitochondrial-targeted photodynamic therapy and fluorescence cell imaging

Abstract

A series of three amphiphilic, mitochondria-targeting cationic boron-dipyrromethene (BODIPY) photosensitizers were synthesized and evaluated for their fluorescence cell imaging and photodynamic therapy (PDT) capabilities. The synthesis involved the reaction of azide-functionalized BODIPY with N,N,N-dimethyloctyl-N-propargyl ammonium bromide via copper-catalyzed azide-alkyne cycloaddition (CuAAC), yielding BODIPYs with hydrophilic cationic regions and lipophilic properties that facilitated mitochondrial targeting. Halogenation of the BODIPY core at the 2 and 6 positions with bromine and iodine reduced fluorescence quantum yields but significantly enhanced singlet oxygen generation due to the heavy atom effect. The dark toxicity and PDT efficacy of these cationic BODIPY photosensitizers were evaluated against two cancer cell lines (MCF-7 and HeLa). Conjugation of the BODIPY backbone with a positively charged, lipophilic octyl ammonium group improved hydrophilicity and facilitated mitochondrial localization, as confirmed by cellular uptake studies. LED light irradiation at the targeted location enhanced cytotoxicity in cancer cells, demonstrating the potential of these photosensitizers for effective anticancer PDT. This study highlights quaternary ammonium-functionalized BODIPY derivatives as promising candidates for photodynamic therapy.