ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Spingler_manuscript_20200622_pSI.pdf (3.93 MB)
0/0

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

preprint
submitted on 22.06.2020 and posted on 24.06.2020 by 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.

Funding

Swiss National Science Fournation 205321_159976

Swiss Government Excellence Scholarship

Novartis Foundation for Medical-Biological Research

ERC Consolidator Grant PhotoMedMet (GA 681679)

Agence National de Recherche, France, ANR-10-IDEX-0001-02 PSL

History

Email Address of Submitting Author

spingler@chem.uzh.ch

Institution

University of Zurich

Country

Switzerland

ORCID For Submitting Author

0000-0003-3402-2016

Declaration of Conflict of Interest

none

Exports