ABSTRACT
Five osmium(II) polypyridyl complexes of the general formula [Os(4,7-diphenyl-1,10-phenanthroline)2 L]2+ were synthesized as photosensitizers for photodynamic therapy by varying the nature of the ligand L. Thanks to the pronounced π-extended structure of the ligands and the heavy atom effect provided by the osmium center, these complexes exhibit a high absorption in the near-infrared (NIR) region (up to 740â nm), unlike related ruthenium complexes. This led to a promising phototoxicity in vitro against cancer cells cultured as 2D cell layers but also in multicellular tumor spheroids upon irradiation at 740â nm. The complex [Os(4,7-diphenyl-1,10-phenanthroline)2 (2,2'-bipyridine)]2+ was found to be the most efficient against various cancer cell lines, with high phototoxicity indexes. Experiments on CT26 tumor-bearing BALB/c mice also indicate that the OsII complexes could significantly reduce tumor growth following 740â nm laser irradiation. The high phototoxicity in the biological window of this structurally simple complex makes it a promising photosensitizer for cancer treatment.
Subject(s)
Coordination Complexes , Neoplasms , Photochemotherapy , Ruthenium , Animals , Mice , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/chemistry , Osmium/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/therapeutic use , Coordination Complexes/chemistry , Neoplasms/drug therapy , Ruthenium/pharmacology , Ruthenium/chemistryABSTRACT
Photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) are therapeutic techniques based on a photosensitizer (PS) and light. These techniques allow the spatial and temporal control of the activation of drugs with light. Transition metal complexes are attractive compounds as photoactivatable prodrugs since their excited states can be appropriately designed by subtle modifications of the ligands, the metal centre, or the oxidation state. However, most metal-based PSs contain heavy metals such as Ru, Os, Ir, Pt or Au, which are expensive and non-earth-abundant, contrary to first-row transition metals. In this context, the exploration of the photochemical properties of complexes based on first-row transition metals appears to be extremely promising. This did encourage several groups to develop promising PSs based on these metals. This review presents up-to-date state-of-the-art information on first-row-transition metal complexes, from titanium to zinc in regard to their application as PSs for phototherapeutic applications.