Ruthenium Porphyrin Compounds for Photodynamic Therapy of Cancer

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• 作者：Fré ; dé ; ric Schmitt ; Padavattan Govindaswamy ; Georg Sü ; ss-Fink ; Wee Han Ang ; Paul J. Dyson ; Lucienne Juillerat-Jeanneret ; Bruno Therrien
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：March 27, 2008
• 年：2008
• 卷：51
• 期：6
• 页码：1811 - 1816
• 全文大小：835K
• 年卷期：v.51,no.6(March 27, 2008)
• ISSN：1520-4804

文摘

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 [Ru₄(η⁶-C₆H₅CH₃)₄(TPP)Cl₈] and [Rh₄(η⁵-C₅Me₅)₄(TPP)Cl₈] 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.