Phototoxicity evaluation of tetra-cationic ruthenium-arene-phosphine porphyrins in ovarian tumor cells.

Photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment, enabling selective cytotoxicity through light-activated photosensitizers. In this work, four tetra-cationic porphyrins and their zinc(II) metalloporphyrin analogues, each coordinated to four peripheral ruthenium(II) arene-phosphine units, were investigated as a new class of compounds (PRAP: Porphyrin-Ruthenium-Arene-Phosphine). The compounds were fully characterized by NMR spectroscopy (1H, 31P, COSY), UV-vis and fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, elemental analysis, and molar conductivity. No significant cytotoxicity toward MRC-5 cells was observed below 25 μM. In contrast, strong phototoxic activity was detected in A2780 ovarian cancer cells following irradiation (415 nm). The free-base porphyrins exhibited higher photodynamic activity (IC₅₀ = 0.06 ± 0.01 μM) than their zinc(II) analogues (IC₅₀ = 0.36 ± 0.08 μM). Among the compounds, H₂P displayed the highest phototoxicity index. Morphological analyses revealed pronounced membrane and nuclear alterations consistent with oxidative stress-induced damage. These findings are supported by ROS generation, apoptosis-related features, and DNA photocleavage activity. Furthermore, photodynamic treatment inhibited spheroid growth in a 3D tumor model, particularly affecting the proliferative outer regions. Overall, PRAP compounds represent a promising platform for developing new photosensitizers for PDT.