Visible Light-Induced Cytotoxicity of a Thiophene–Benzothiadiazole-Based Conjugated Oligoelectrolyte in Cancer Cells

We report the in vitro visible-light-induced cytotoxic activity of a donor-acceptor-donor π-conjugated oligoelectrolyte <b>M1,</b> in which a 4,7-dithiophene benzothiadiazole core is flanked by phenyl rings with ionic side chains. The π-electron delocalized framework with electron-rich and electron-deficient moieties provides <b>M1</b> with strong light absorption in the midvisible region (∼500 nm). The presence of a hydrophobic core with cationic quaternary ammonium side chains at its six terminals introduces amphiphilicity to <b>M1</b>, making it water-soluble and hence biologically compatible. <b>M1</b> displays efficient penetration into breast and ovarian cancer cells (HCC1937, OVCAR-8, and SK-OV-3) with localization determined by confocal laser scanning microscopy, indicative of endosomal trafficking. Light activation of cancer cells preloaded with 10 μM <b>M1</b> using a 525 nm source (4.5 mW/cm²) for 5 min promoted a significant reduction in cell viability that was not observed under dark conditions, when cells were subject to light in the absence of <b>M1</b>, or when <b>M1</b> was activated prior to cellular uptake. Spectroscopic investigations point toward the ability of <b>M1</b> to sensitize singlet oxygen (¹O₂) as the in situ generated reactive oxygen species (Φ ∼ 0.15) that effectively leads to cancer cell death, specifically in cells containing intracellular <b>M1</b> at the time of light activation, providing a platform that can be targeted to cancer cells to provide selective phototoxicity at wavelengths compatible with biological systems.