Fiche publication
Date publication
juillet 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel
,
Dr FROCHOT Céline
,
Pr SCHNEIDER Raphaël
Tous les auteurs :
Gravier J, Schneider R, Frochot C, Bastogne T, Schmitt F, Didelon J, Guillemin F, Barberi-Heyob M
Lien Pubmed
Résumé
The cell membrane folate receptor (FR) is a molecular target for tumor-selective drug delivery, including delivery of photosensitizers for anticancer photodynamic therapy (PDT). Tumor selectivity of meta-tetra(hydroxyphenyl)chlorin ( m-THPC), a photosensitizer used in PDT clinical trials, demonstrates a low tumor-to-normal epithelial uptake ratio. We report on the synthesis and on the photophysical properties of a m-THPC-like photosensitizer 1 conjugated to folic acid (compound 8). A comparative study of the accumulation of photosensitizers 1 and 8 is described. Nude mice were xenografted with FR-alpha-positive KB or HT-29 cells lacking FR-alpha as a negative control. Using optical fiber fluorimetry, we demonstrated that conjugate 8 exhibited enhanced accumulation in KB tumors compared to 1 4 h after injection. No significant difference between KB and HT-29 tumors was observed in case of compound 1. Tumor-to-normal tissue ratio exhibited a very interesting selectivity for conjugate 8 (5:1) in KB tumors 4 h postinjection.
Référence
J Med Chem. 2008 Jul 10;51(13):3867-77
