title: Photocytotoxicity of a cyanine dye with two chromophores toward melanoma and normal cells.
abstract: BACKGROUND
  Due to high optical absorption, triplet quantum yield and affinity to biological structures bichromophoric cyanine dyes (BCDs) can be considered promising sensitizers for application in photodynamic therapy (PDT). In this work, we report on the study of the BCD photocytotoxicity toward melanoma and normal cells in comparison with that of commercial photosensitizer Photogem®.
  
  
  METHODS
  The cytotoxic and phototoxic effects were measured by standard tests of cell viability. The drug uptake was obtained by the flow cytometry and optical absorption techniques. The BCD intracellular distribution was obtained by the fluorescence image microscopy using specific organelle markers.
  
  
  RESULTS
  Both drugs demonstrated increased cytotoxicity under irradiation, while in darkness their cytotoxic effect at concentrations lower than 20 μM after 24 h of incubation did not exceed 20%. For 5 h of incubation, BCD photocytotoxicity in relation to melanoma cells reached 100% already at concentrations below 5 μM, while for normal cells the effect did not exceed 70% even for the 20 μM concentration. It is shown that BCD penetrates into the cells and is located predominantly in perinuclear cytoplasmic structures.
  
  
  CONCLUSIONS
  The BCD photosensitizing characteristics appear more adequate for application in PDT than that of the actually applied commercial photosensitizer Photogem®. Higher light absorption by BCD in the near IR region and its preferential localization in mitochondria can explain its high photocytotoxicity.
  
  
  CONCLUSIONS
  BCD can be considered as a new promising photosensitizer class for cancer PDT.
authors.affiliation: Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, CEP 14040-901 Ribeirão Preto, SP, Brazil.
authors.forename: L S
authors.initials: LS
authors.lastname: Murakami
authors.affiliation: Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, CEP 14040-901 Ribeirão Preto, SP, Brazil.
authors.forename: L P
authors.initials: LP
authors.lastname: Ferreira
authors.affiliation: Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Prof. Zeferino Vaz s/n, CEP 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: J S
authors.initials: JS
authors.lastname: Santos
authors.affiliation: Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Prof. Zeferino Vaz s/n, CEP 14040-903 Ribeirão Preto, SP, Brazil; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, CEP 14040-901 Ribeirão Preto, SP, Brazil.
authors.forename: R S
authors.initials: RS
authors.lastname: da Silva
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Prof. Zeferino Vaz s/n, CEP 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Nomizo
authors.affiliation: Emanuel Institute of Biochemical Physics, Russian Academy of Science, Kosygin St, 4, 117977 Moscow, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Kuz'min
authors.affiliation: Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, CEP 14040-901 Ribeirão Preto, SP, Brazil. Electronic address: iouribor@usp.br.
authors.forename: I E
authors.initials: IE
authors.lastname: Borissevitch
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism / Q000494:pharmacology*; D006415:Hematoporphyrins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D010539:Permeability; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C000600679:BCD cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D006415:Hematoporphyrins; C000600680:Photogem; D017319:Photosensitizing Agents
keywords: Bichromophoric cyanine dye; Melanoma; Normal cell; Photocytotoxicity