title: Photocytotoxic activity of a nitrosyl phthalocyanine ruthenium complex--a system capable of producing nitric oxide and singlet oxygen.
abstract: The synthesis, structural aspects, pharmacological assays, and in vitro photoinduced cytotoxic properties of [Ru(NO)(ONO)(pc)] (pc=phthalocyanine) are described. Its biological effect on the B16F10 cell line was studied in the presence and absence of visible light irradiation. At comparable irradiation levels, [Ru(NO)(ONO)(pc)] was more effective than [Ru(pc)] at inhibiting cell growth, suggesting that occurrence of nitric oxide release following singlet oxygen production upon light irradiation may be an important mechanism by which the nitrosyl ruthenium complex exhibits enhanced biological activity in cells. Following visible light activation, the [Ru(NO)(ONO)(pc)] complex displayed increased potency in B16F10 cells upon modifications to the photoinduced dose; indeed, enhanced potency was detected when the nitrosyl ruthenium complex was encapsulated in a drug delivery system. The liposome containing the [Ru(NO)(ONO)(pc)] complex was over 25% more active than the corresponding ruthenium complex in phosphate buffer solution. The activity of the complex was directly proportional to the ruthenium amount present inside the cell, as determined by inductively coupled plasma mass spectroscopy. Flow cytometry analysis revealed that the photocytotoxic activity was mainly due to apoptosis. Furthermore, the vasorelaxation induced by [Ru(NO)(ONO)(pc)], proposed as NO carrier, was studied in rat isolated aorta. The observed vasodilation was concentration-dependent. Taken together, the present findings demonstrate that the [Ru(NO)(ONO)(pc)] complex induces vascular relaxation and could be a potent anti-tumor agent. Nitric oxide release following singlet oxygen production upon visible light irradiation on a nitrosyl ruthenium complex produces two radicals and may elicit phototoxic responses that may find useful applications in photodynamic therapy.
authors: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil.
authors: Zumira Aparecida
authors: ZA
authors: Carneiro
authors: Juliana Cristina Biazzotto
authors: JC
authors: de Moraes
authors: Fernando Postalli
authors: FP
authors: Rodrigues
authors: Renata Galvão
authors: RG
authors: de Lima
authors: Carlos
authors: C
authors: Curti
authors: Zênis Novaes
authors: ZN
authors: da Rocha
authors: Michele
authors: M
authors: Paulo
authors: Lusiane Maria
authors: LM
authors: Bendhack
authors: Antonio Claudio
authors: AC
authors: Tedesco
authors: André Luiz Barboza
authors: AL
authors: Formiga
authors: Roberto Santana
authors: RS
authors: da Silva
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D008297:Male; D008665:Metalloporphyrins / Q000737:chemistry* / Q000633:toxicity*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D026082:Singlet Oxygen / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D008665:Metalloporphyrins; D009942:Organometallic Compounds; C528283:ruthenium phthalocyanine; D026082:Singlet Oxygen; D009569:Nitric Oxide