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

Int J Mol Sci. 2023 Sep 2;24(17):13614. doi: 10.3390/ijms241713614.

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.

Keywords: apoptosis; arene–ruthenium complexes; photodynamic therapy; photosensitizers; prostate cancer.

MeSH terms

  • Animals
  • Apoptosis
  • Drug-Related Side Effects and Adverse Reactions*
  • Gastropoda*
  • Humans
  • Male
  • Neoplasms, Second Primary*
  • Photosensitizing Agents / pharmacology
  • Prostatic Neoplasms* / drug therapy
  • Ruthenium* / pharmacology

Substances

  • Photosensitizing Agents
  • Ruthenium

Grants and funding

This research was funded by Ministère de l’Enseignement Supérieur et de la Recherche Scientifique of France, Région Nouvelle-Aquitaine and Ligue contre le Cancer (Comité départemental 87—Haute-Vienne).