Metabolic profile and in vivo stability of a peptide-conjugated chlorin-type photosensitiser targeting neuropilin-1 : Interest of pseudopeptides. - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2007

Metabolic profile and in vivo stability of a peptide-conjugated chlorin-type photosensitiser targeting neuropilin-1 : Interest of pseudopeptides.

Résumé

Destruction of the neovasculature is essential for efficient tumour eradication by photodynamic therapy (PDT). Since the over-expression of Vascular Endothelial Growth Factor (VEGF) receptors is correlated with tumour angiogenesis and growth, we conjugated a photosensitiser (5-4-carboxyphenyl)-10,15,20-triphenyl-chlorin, TPC) via a spacer (6-aminohexanoic acid, Ahx) to a neuropilin-1 (NRP-1) specific homing heptapeptide (ATWLPPR) targeting tumour vasculature (Tirand et al. 2006). The intratumoural localisation of the photosensitiser, its stability and its metabolic profile have been studied on a model of nude mice xenografted with U87 human malignant glioma cells (Tirand et al. 2007). By fluorescence microscopy, we evidenced a selective accumulation of the conjugated photosensitiser in the endothelial cells bordering the tumour vessels compared with unconjugated photosensitiser. TPC-Ahx-ATWLPPR accumulated at high levels in the tumour and tissues of the reticuloendothelial system, particularly by liver and spleen. TPC-Ahx-ATWLPPR was stable in vitro in plasma for at least 24 h at 37°C. In vivo, the peptide moiety was progressively degraded from 2h post injection, resulting in the formation of a metabolic product, TPC-Ahx-A (Tirand, et al. 2007). In order to improve the heptapeptide stability towards proteases (Adessi and Soto 2002) and to avoid any non-selective accumulation of the metabolic product, this photosensitiser has been coupled to pseudopeptides on solid support. We have, for the first time, studied the affinity of these pseudopeptides towards the different VEGF165 (isoform 165 of VEGF) receptors (NRP-1, NRP-2, Flt-1 and KDR) by competition experiments. .

Domaines

Biophysique
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Dates et versions

hal-00167550 , version 1 (21-08-2007)

Identifiants

  • HAL Id : hal-00167550 , version 1

Citer

Noémie Thomas, Loraine Tirand, Régis Vanderesse, François Plénat, François Guillemin, et al.. Metabolic profile and in vivo stability of a peptide-conjugated chlorin-type photosensitiser targeting neuropilin-1 : Interest of pseudopeptides.. 12th Congress of the European Society for Photobiology, Sep 2007, Bath, United Kingdom. ⟨hal-00167550⟩
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