Fiche publication
Date publication
mai 2025
Journal
Inorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GAIDDON Christian
,
Dr MELLITZER Georg
Tous les auteurs :
Restrepo-Acevedo A, Murillo MI, Orvain C, Thibaudeau C, Recberlik S, Verget L, Gómez Vidales V, Gaiddon C, Mellitzer G, Le Lagadec R
Lien Pubmed
Résumé
In recent years, photodynamic therapy (PDT) has emerged as a promising alternative to classical chemotherapy for treating cancer. PDT is based on a nontoxic prodrug called photosensitizer (PS) activated by light at the desired location. Upon irradiation, the PS reacts with the oxygen present in the tumor, producing cytotoxic reactive oxygen species (ROS). Compounds with highly conjugated π-bond systems, such as porphyrins and chlorins, have proven to be excellent light scavengers, and introducing a metal atom in their structure improved the generation of ROS. In this work, a series of tetrapyrrole-ruthenium(II) complexes derived from protoporphyrin IX and the commercial drug verteporfin were designed as photosensitizers for PDT. The complexes were almost nontoxic on human gastric cancer cells under dark conditions, revealing remarkable cytotoxicity upon irradiation with light. The ruthenium atom in the central cavity of the chlorin ligand allowed combined mechanisms in photodynamic therapy, as both singlet oxygen and superoxide radicals were detected. Additionally, one complex produced large amounts of singlet oxygen under hypoxic conditions. Biological assays demonstrated that the ruthenium derivatives caused cell death through a caspase 3 mediated apoptotic pathway and CHOP, an endoplasmic reticulum stress-inducible transcription factor involved in apoptosis and growth arrest.
Référence
Inorg Chem. 2025 05 2;:
