PVP formulations of bis-cyclometalated iridium(III) complexes bearing β-modified porphyrin ligands: characterization and photodynamic action on bladder cancer cells

Cancer stands as the second leading global cause of death, following heart disease. Considering the severe side effects revealed by some chemotherapeutics for tumor treatment and anticancer therapies, the scientific community is actively exploring more effective alternatives. Photodynamic Therapy (PDT) mediated by porphyrin-based photosensitizers (PS) has emerged as an attractive alternative to more conventional therapies. In this study, we incorporated bis-cyclometalated iridium(III) complexes featuring porphyrin-arylbipyridine ligands into poly(vinylpyrrolidone) (PVP) micelle. This integration resulted in photostable PVP-PS formulations with a remarkable capability to generate singlet oxygen. These formulations were also efficiently internalized by HT-1379 cells and due to these features, their photodynamic action against human bladder cancer cells (HT-1376 cell line) was assessed. All the formulations demonstrated high photodynamic activity, with PVP-2 and PVP-3 proving to be the most promising PS, as evidenced by their lower IC50_PDT values. It was also demonstrated that all PVP-based formulations provide a safe and effective approach for photodynamic therapy (PDT) in bladder cancer, as no cytotoxic effects were observed in Vero cells.