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Spingler_manuscript_20200622_pSI.pdf (3.93 MB)
Studying the Cellular Distribution of Highly Phototoxic Platinated Metalloporphyrins Using Isotope Labelling
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 22.06.2020 and posted on 24.06.2020by Riccardo Rubbiani, Wenyu Wu, Anu Naik, Michele Larocca, Lukas Schneider, Roxane Padrutt, Vipin Babu, Christiane König, Doris Hinger, Caroline Maake, Stefano Ferrari, Gilles Gasser, Bernhard Spingler
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.