Investigation of in vitro photodynamic activities of PEG and glycosyl group substituted BODIPY compounds

Photodynamic therapy (PDT) is a minimally invasive treatment modality that eliminates tumor cells through the light-induced generation of reactive oxygen species (ROS). The therapeutic efficacy of PDT depends on the photophysical performance, stability, and biological compatibility of the photosensitizer. In the present study, previously developed PEG- and glycosyl-functionalized BODIPY derivatives (PS1 and PS2) were systematically evaluated for their suitability as photosensitizers in PDT. Singlet oxygen quantum yields, photodegradation efficiencies, and aggregation behavior were determined to assess their photochemical performance. Their in vitro photodynamic activities were investigated in HT29 colorectal cancer cells and HUVEC endothelial cells. In addition to cytotoxic evaluation, global DNA methylation (5-mC) levels were quantified using an ELISA-based assay to explore potential epigenetic effects associated with photodynamic activation. Both PS1 and PS2 exhibited favorable photostability, efficient singlet oxygen generation, low dark toxicity, and significant light-induced reduction in HT29 cell viability. Notably, photoactivated treatment was associated with a significant decrease in global DNA methylation levels in HT29 cells, whereas no significant changes were observed in non-tumoral HUVEC cells. Although a direct causal relationship cannot be established, these findings suggest a potential interplay between ROS-mediated cytotoxicity and epigenetic modulation. By integrating photophysical characterization with biological and epigenetic evaluation, this study provides a broader perspective on the functional impact of PEG- and glycosyl-modified BODIPY photosensitizers in PDT.