Fiche publication
Date publication
juin 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel
,
Dr FROCHOT Céline
,
Dr VANDERESSE Régis
Tous les auteurs :
Frochot C, Di Stasio B, Vanderesse R, Belgy MJ, Dodeller M, Guillemin F, Viriot ML, Barberi-Heyob M
Lien Pubmed
Résumé
Destruction of the neovasculature is essential for tumor eradication by photodynamic therapy. Since the over-expression of integrins is correlated with tumor angiogenesis, we conjugated a photosensitizer (5-(4-carboxyphenyl)-10,15,20-triphenylchlorin or porphyrin) to the alpha(v)beta(3) integrin specific peptide RGD (H-Arg-Gly-Asp-OH) motif as a common sequence. We reported an efficient solid-phase synthesis of a new family of peptidic photosensitizers with linear or cyclic[RGDfK] RGD motif and compared conjugates in vitro selectivity and photodynamic activity. The conjugates were characterized by (1)H NMR, MALDI, UV-visible spectroscopy and singlet oxygen formation was performed. Chlorins containing linear and constrained RGD motif were incorporated up to 98- and 80-fold more, respectively, than the unconjugated photosensitizer over a 24-h exposure in human umbilical vein endothelial cells (HUVEC) over-expressing alpha(v)beta(3) integrin. Peptidic moiety also led to a non-specific increased cellular uptake by murine mammary carcinoma cells (EMT-6), lacking RGD binding receptors. Survival measurements demonstrated that HUVEC were greatly sensitive to conjugates-mediated photodynamic therapy.
Référence
Bioorg Chem. 2007 Jun;35(3):205-20
