Photodynamic activity of a mitochondria-localized G-quadruplex-responsive fluorescent ligand: Cellular effects and photo-enhanced cytotoxicity.

Abstract

Mitochondrial localization concentrates photosensitizing molecules near redox-sensitive organelles. In this study, we investigated SPN, a mitochondria-targeted G-quadruplex (G4)-responsive ligand. Photochemical characterization confirmed that SPN generates robust light-triggered ROS and exhibits photooxidative activity in vitro. In cancer cell models under dark conditions, SPN treatment was associated with cell-cycle perturbation, loss of mitochondrial membrane potential, altered mitochondrial morphology, elevated mitochondrial superoxide-sensitive fluorescence, and accumulation of MDC-positive autophagic vacuoles. White-light irradiation markedly enhanced intracellular oxidation-sensitive fluorescence and reduced cell viability at shorter incubation times and lower SPN concentrations. Mechanistically, SPN plus light was associated with reduced NDUFB8 and SDHB abundance and increased cleaved caspase-3 levels, consistent with mitochondrial respiratory chain perturbation and apoptotic signaling. Collectively, these results establish the photodynamic activity of SPN and identify mitochondrial stress and caspase-3-associated apoptosis as central components of its cellular response.