Effects of metalation on the PDT activity of arene ruthenium porphyrin-based photosensitizers on prostate cancer

Significance Prostate cancer is a major health issue (second most common cancer in men worldwide). Despite therapeutic advances and early detection, many side effects are often observed during treatment. Photodynamic therapy (PDT) is a promising therapy to reduce side effects, many 2nd and 3rd generation of photosensitizer (PS) are poorly soluble in aqueous media, limiting their attractiveness. Approach We have developed and tested 3rd generation of PS vectorized by arene-ruthenium (Ru) complexes coordinated to tetrapyridylporphin (tpp-2H), Zn-tetrapyridylporphin (tpp-Zn) or Co-tetrapyridylporphin (tpp-Co). Results Two of the three complexes show a good efficacy. The compounds localize into the cytoplasm. An analysis of the apoptotic process shows a cleavage of poly-ADP ribose polymerase (PARP) and a strong induction of DNA fragmentation following irradiation. Conclusions Arene-ruthenium tetrapyridylporphin complexes are excellent candidates for PDT application. The addition of the metal shows a decrease (tpp-Zn) or no effects (tpp-Co), compared to the metal free photosentizer (tpp-2H).