Ruthenium porphyrin compounds for photodynamic therapy of cancer.
Five 5,10,15,20-tetra(4-pyridyl)porphyrin (TPP) areneruthenium(II) derivatives and a p-cymeneosmium and two pentamethylcyclopentadienyliridium and -rhodium analogues were prepared and characterized as potential photosensitizing chemotherapeutic agents. The biological effects of all these derivatives were assessed on human melanoma tumor cells, and their cellular uptake and intracellular localization were determined. All molecules, except the rhodium complex which was not cytotoxic, demonstrated comparable cytotoxicity in the absence of laser irradiation. The ruthenium complexes exhibited excellent phototoxicities toward melanoma cells when exposed to laser light at 652 nm. Cellular uptake and localization microscopy studies of [Ru 4(eta (6)-C 6H 5CH 3) 4(TPP)Cl 8] and [Rh 4(eta (5)-C 5Me 5) 4(TPP)Cl 8] revealed that they accumulated in the melanoma cell cytoplasm in granular structures different from lysosomes. The fluorescent porphyrin moiety and the metal component were localized in similar structures within the cells. Thus, the porphyrin areneruthenium(II) derivatives represent a promising new class of organometallic photosensitizers able to combine chemotherapeutic activity with photodynamic therapeutic treatment of cancer.
Schmitt
Frédéric
F
Institute of Pathology, University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
Govindaswamy
Padavattan
P
Süss-Fink
Georg
G
Ang
Wee Han
WH
Dyson
Paul J
PJ
Juillerat-Jeanneret
Lucienne
L
Therrien
Bruno
B
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007834:Lasers; D008247:Lysosomes / Q000737:chemistry; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D011166:Porphyrins / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; D012428:Ruthenium