Studying the Cellular Distribution of Highly Phototoxic Platinated Metalloporphyrins Using Isotope Labelling

We report the synthesis of novel tetraplatinated metalloporphyrin-based photosensitizers (PSs) for photodynamic therapy (PDT), their characterization, cellular uptake and localization, as well as the determination of their in vitro light-induced anticancer properties. The PSs show excellent phototoxic indexes up to 5800 against HeLa cells, which is, to the best of our knowledge, the highest value reported for any porphyrin so far. Furthermore, isotopic labelling of the porphyrin with a highly enriched ⁶⁷Zn isotope was performed in order to determine the distribution ratio of zinc to platinum by ICP-MS, allowing to differentiate between naturally occurring zinc and ⁶⁷Zn that was introduced into the cells by the PS. We conclude that the platinum units within the platinum-PS conjugates help to solubilize the PS and, at the same time, act as cell-penetrating vectors, enhancing the efficiency of the PS without causing a significant dark toxicity.