Publication

Ruthenium Porphyrin Compounds for Photodynamic Therapy of Cancer

Paul Joseph Dyson, Wee Han Ang, Frédéric Schmitt
2008
Journal Articles

Abstract

Five 5,10,15,20-tetra(4-pyridyl)porphyrin (TPP) areneruthenium(II) derivs., a p-cymeneosmium, a pentamethylcyclopentadienyliridium and a pentamethylcyclopentadienylrhodium analog were prepd. and characterized as potential photosensitizing chemotherapeutic agents. The dinuclear areneruthenium complexes [Ru(h6-arene)(m-Cl)Cl]2 (arene = C6H6, C6H5CH3, p-iPrC6H4Me, C6Me6, and 1,4-C6H4(COOEt)2) react with TPP in MeOH to give the corresponding tetranuclear complexes [Ru4(h6-arene)4(TPP)Cl8] (arene = C6H6 (1, 56% yield), C6H5CH3 (2, 70%), p-iPrC6H4Me (3, 70%), C6Me6 (4, 79%), 1,4-C6H4(COOEt)2 (5, 73%)). The dinuclear p-cymeneosmium complex [Os(h6-p-iPrC6H4Me)(m-Cl)Cl]2 reacts with TPP to form the tetranuclear areneosmium complex [Os4(h6-p-iPrC6H4Me)4(TPP)Cl8] (6) in 47% yield. The isoelectronic Rh and Ir pentamethylcyclopentadienyl derivs. [Rh4(h5-C3Me5)4(TPP)Cl8] (7, 73%) and [Ir4(h5-C3Me5)4(TPP)Cl8] (8, 83%) were obtained in MeOH from the reaction of [M(h5-C5Me5)(m-Cl)Cl]2 (M = Rh, Ir) with TPP. The mol. structures of 4 and 7 were detd. by x-ray crystallog. The biol. effects of all these derivs. were assessed on human melanoma tumor cells, and their cellular uptake and intracellular localization were detd. All mols., except the Rh complex which was not cytotoxic, demonstrated comparable cytotoxicity in the absence of laser irradn. The Ru complexes exhibited excellent phototoxicities toward melanoma cells when exposed to laser light at 652 nm. Cellular uptake and localization microscopy studies of [Ru4(h6-C6H5CH3)4(TPP)Cl8] and [Rh4(h5-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) derivs. represent a promising new class of organometallic photosensitizers able to combine chemotherapeutic activity with photodynamic therapeutic treatment of cancer.

Official source

Paul Joseph Dyson, Wee Han Ang, Frédéric Schmitt
2008
Journal Articles

Abstract

Official source

Related concepts (26)

Melanoma

Melanoma, also redundantly known as malignant melanoma, is a type of cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In women, they most commonly occur on the legs, while in men, they most commonly occur on the back. About 25% of melanomas develop from moles. Changes in a mole that can indicate melanoma include an increase in size, irregular edges, change in color, itchiness, or skin breakdown.

Photodynamic therapy

Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance, used in conjunction with molecular oxygen to elicit cell death (phototoxicity). PDT is popularly used in treating acne. It is used clinically to treat a wide range of medical conditions, including wet age-related macular degeneration, psoriasis, atherosclerosis and has shown some efficacy in anti-viral treatments, including herpes. It also treats malignant cancers including head and neck, lung, bladder and particular skin.

Skin cancer

Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC), squamous-cell skin cancer (SCC) and melanoma. The first two, along with a number of less common skin cancers, are known as nonmelanoma skin cancer (NMSC). Basal-cell cancer grows slowly and can damage the tissue around it but is unlikely to spread to distant areas or result in death.

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