Titre | Interest of RGD-containing linear or cyclic peptide targeted tetraphenylchlorin as novel photosensitizers for selective photodynamic activity. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Frochot, C, Di Stasio, B, Vanderesse, R, Belgy, M-J, Dodeller, M, Guillemin, F, Viriot, M-L, Barberi-Heyob, M |
Journal | Bioorg Chem |
Volume | 35 |
Issue | 3 |
Pagination | 205-20 |
Date Published | 2007 Jun |
ISSN | 0045-2068 |
Mots-clés | Animals, Cell Line, Cell Survival, Drug Screening Assays, Antitumor, Endothelial Cells, Humans, Integrin alphaVbeta3, Mammary Neoplasms, Animal, Mice, Molecular Structure, Peptides, Peptides, Cyclic, Photochemotherapy, Photosensitizing Agents, Porphyrins, Structure-Activity Relationship |
Abstract | 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. |
DOI | 10.1016/j.bioorg.2006.11.005 |
Alternate Journal | Bioorg. Chem. |
PubMed ID | 17223161 |