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Communication Dans Un Congrès Année : 2008

Metabolic profile of a peptide-conjugated chlorin-type photosensitizer targeting neuropilin-1: an in vivo and in vitro study

Résumé

Since angiogenic endothelial cells of the tumor vasculature represent an interesting target to potentiate the vascular effect of photodynamic therapy, we recently described the conjugation of a photosensitizer (5-(4-carboxyphenyl)-10,15,20-triphenylchlorin,TPC), via a spacer (6-aminohexanoic acid, Ahx), to a VEGF receptor-specific heptapeptide (ATWLPPR), and demonstrated that TPC-Ahx-ATWLPPR binds to neuropilin-1. TPC-Ahx-ATWLPPR was stable in vitro in human and mouse plasma for at least 24 h at 37 ◦C but, following intravenous injection in glioma-bearing nude mice, was degraded in vivo to various rates, depending on the organ considered. TPC-Ahx-A was identified as the main metabolic product and pharmacokinetic studies suggested that its appearance in plasma mainly resulted from the degradation of the peptidic moiety into organs of the reticuloendothelial system. According to in vitro cell culture experiments, TPC-Ahx-ATWLPPR was also significantly degraded after incorporation in human umbilical vein endothelial cells. As we demonstrated that TPC-Ahx-ATWLPPR mostly localized into lysosomes, HUVEC were treated with the lysosomal enzymes inhibitor ammonium chloride, which resulted in a significant decrease of the peptide degradation. But, taken together, our results suggest that the low levels of degradation observed in plasma, tumor and skin, are not likely to have a negative impact on our tumor-targeting photosensitizer strategy.

Domaines

Biophysique
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Dates et versions

hal-00323710 , version 1 (23-09-2008)

Identifiants

  • HAL Id : hal-00323710 , version 1

Citer

Noémie Thomas, Loraine Tirand, Céline Frochot, François Guillemin, Muriel Barberi-Heyob. Metabolic profile of a peptide-conjugated chlorin-type photosensitizer targeting neuropilin-1: an in vivo and in vitro study. 1st Conference of the European Platform for Photodynamic Medicine, EPPM-1, Mar 2008, Dubrovnic, Croatia. ⟨hal-00323710⟩
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