The Effect of Photosensitizer Metalation Incorporated into Arene–Ruthenium Assemblies on Prostate Cancer

Author:

Paulus Lucie1,Gallardo-Villagrán Manuel12,Carrion Claire3,Ouk Catherine3,Martin Frédérique1,Therrien Bruno2ORCID,Léger David Yannick1,Liagre Bertrand1ORCID

Affiliation:

1. Univ. Limoges, LABCiS, UR 22722, Faculté de Pharmacie, F-87000 Limoges, France

2. Institut de Chimie, Université de Neuchâtel, Avenue de Bellevaux 51, CH-2000 Neuchâtel, Switzerland

3. Univ. Limoges, CNRS, Inserm, CHU Limoges, BISCEm, UAR 2015, US 42, F-87000 Limoges, France

Abstract

Prostate cancer is the second most common cancer for men and a major health issue. Despite treatments, a lot of side effects are observed. Photodynamic therapy is a non-invasive method that uses photosensitizers and light to induce cell death through the intramolecular generation of reactive oxygen species, having almost no side effects. However, some of the PSs used in PDT show inherent low solubility in biological media, and accordingly, functionalization or vectorization is needed to ensure internalization. To this end, we have used arene–ruthenium cages in order to deliver PSs to cancer cells. These metalla-assemblies can host PSs inside their cavity or be constructed with PS building blocks. In this study, we wanted to determine if the addition of metals (Mg, Co, Zn) in the center of these PSs plays a role. Our results show that most of the compounds induce cytotoxic effects on DU 145 and PC-3 human prostate cancer cells. Localization by fluorescence confirms the internalization of the assemblies in the cytoplasm. An analysis of apoptotic processes shows a cleavage of pro-caspase-3 and poly-ADP-ribose polymerase, thus leading to a strong induction of DNA fragmentation. Finally, the presence of metals in the PS decreases PDT’s effect and can even annihilate it.

Funder

Ministère de l’Enseignement Supérieur et de la Recherche Scientifique of France, Région Nouvelle-Aquitaine

Ligue contre le Cancer

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference38 articles.

1. (2023, April 11). Cancer Today. Available online: http://gco.iarc.fr/today/home.

2. EAU (2023, July 19). Guidelines on Prostate Cancer—Uroweb. Available online: https://uroweb.org/guidelines/prostate-cancer.

3. Erectile Function after Focal Therapy for Localized Prostate Cancer: A Systematic Review;Fallara;Int. J. Impot. Res.,2021

4. Treatment Effects in Prostate Cancer;Evans;Mod. Pathol.,2018

5. Malinowski, B., Wiciński, M., Musiała, N., Osowska, I., and Szostak, M. (2019). Previous, Current, and Future Pharmacotherapy and Diagnosis of Prostate Cancer—A Comprehensive Review. Diagnostics, 9.

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