title: In vitro phototoxicity of glycoconjugated porphyrins and chlorins in colorectal adenocarcinoma (HT29) and retinoblastoma (Y79) cell lines.
abstract: BACKGROUND
  Retinoblastoma is the most common malignant intraocular tumor in children. The current treatment gives a good vital prognostic but there are several drawbacks to the arsenal of "classical antitumoral" therapies. Photodynamic therapy (PDT) could be an exciting non-toxic and non-mutagenic alternative protocol.
  
  
  METHODS
  In this paper, we report about the screening of the in vitro photocytotoxicity of hydrophenylporphyrins and chlorins and their glycoconjugated derivatives in a human retinoblastoma cell line (Y79) and for comparison in a colorectal adenocarcinoma cell line (HT29).
  
  
  RESULTS
  Despite lower photodynamic activity than that observed for hydroxylated photosensitizers, in particular Foscan(®) glycoconjugated derivatives display phototoxicity (IC50 2.4-0.05μM ±10%) against Y79 cells with examples of significant intrinsic cytotoxicity. Amongst them the triglucosyl porphyrin 10 is highly photocytotoxic (IC50 0.9μM ±10%) but is fully devoid of cytotoxicity (IC50>15μM). The photoactivity is highly modulated by the presence of a diethyleneglycol spacer between the chromophore and the glycoside (compounds 14-17, IC50 0.5, 0.6, 0.05 and 0.35μM ±10%) and by the anomeric configuration of the sugar (compound 15 and 17, IC50 0.6 and 0.05μM ±10% respectively). One of the main problems for the use of Foscan(®) is its poor solubility which might be improved by glycoconjugation. Moreover Foscan has been shown to induce necrosis after PDT leading to a possible ulceration of surrounding tissues unsuitable for a conservative treatment. A preferential mitochondrial subcellular localization which has been previously reported for some glycoconjugated photosensitizers could enhance the contribution of apoptosis process.
  
  
  CONCLUSIONS
  Tri-α-O-galactosyl porphyrin 16 is a better candidate than Foscan(®) for a clinical application of PDT for a conservative therapy of retinoblastoma.
authors.affiliation: UMR 176 CNRS, Institut Curie, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France; Institut Curie, Section de Recherches, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France.
authors.forename: Ph
authors.initials: P
authors.lastname: Maillard
authors.affiliation: UMR 176 CNRS, Institut Curie, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France; Institut Curie, Section de Recherches, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France.
authors.forename: B
authors.initials: B
authors.lastname: Loock
authors.affiliation: UMR 176 CNRS, Institut Curie, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France; Institut Curie, Section de Recherches, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France.
authors.forename: D S
authors.initials: DS
authors.lastname: Grierson
authors.affiliation: BIOMOCETI, UMR CNRS 7033/Université Pierre et Marie Curie, 2 place Jussieux, Univ P. et M. Curie, Paris F-75005, France.
authors.forename: I
authors.initials: I
authors.lastname: Laville
authors.affiliation: BIOMOCETI, UMR CNRS 7033/Université Pierre et Marie Curie, 2 place Jussieux, Univ P. et M. Curie, Paris F-75005, France.
authors.forename: J
authors.initials: J
authors.lastname: Blais
authors.affiliation: Oncologie Pédiatrique, Ophtalmologie, Hôpital Cl. Regaud, 26 rue d'Ulm, Institut Curie, Paris F-75005, France.
authors.forename: F
authors.initials: F
authors.lastname: Doz
authors.affiliation: Oncologie Pédiatrique, Ophtalmologie, Hôpital Cl. Regaud, 26 rue d'Ulm, Institut Curie, Paris F-75005, France.
authors.forename: L
authors.initials: L
authors.lastname: Desjardins
authors.affiliation: Institut Curie, Section de Recherches, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France; Inserm Unité 759 Institut Curie, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France.
authors.forename: D
authors.initials: D
authors.lastname: Carrez
authors.affiliation: Institut Curie, Section de Recherches, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France; Inserm Unité 759 Institut Curie, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Guerquin-Kern
authors.affiliation: Institut Curie, Section de Recherches, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France; Inserm Unité 759 Institut Curie, Centre Universitaire, Univ Paris-Sud, Orsay, F-91405, France.
authors.forename: A
authors.initials: A
authors.lastname: Croisy