Peptide-conjugated chlorin-type photosensitizer binds neuropilin-1 in vitro and in vivo.

Abstract

The strategy developed aims to favor the vascular effect of photodynamic therapy (PDT) by targeting tumor vasculature. This approach is considered by coupling a photosensitizer (PS) to an heptapeptide targeting neuropilin-1 (NRP-1). We previously demonstrated that this new conjugated PS, which binds to recombinant NRP-1 protein, was a much more potent PS compared to the non-conjugated PS in human umbilical vein endothelial cells (HUVEC) expressing NRP-1, due to the coupling of the peptide moiety. To argue the involvement of NRP-1 in the conjugated PS cellular uptake, MDA-MB-231 breast cancer cells were used, strongly over-expressing NRP-1 receptor, and we evidenced a significant decrease of the conjugated PS uptake after RNA interference-mediated silencing of NRP-1. In mice xenografted ectopically with U87 human malignant glioma cells, we demonstrated that only the conjugated PS allowed a selective accumulation in endothelial cells lining tumor vessels. Vascular endothelial growth factor (VEGF) plasma and tumor levels could not prevent the recognition of the conjugate by NRP-1. The vascular effect induced by the conjugated PS, was characterized by a reduction in tumor blood flow around 50% during PDT. In vivo, the photodynamic efficiency with the conjugated PS induced a statistically significant tumor growth delay compared to the non-coupled PS. The peptide-conjugated chlorin-type PS uptake involves NRP-1 and this targeting strategy favors the vascular effect of PDT in vivo.

DOI: 10.1016/j.jphotobiol.2009.04.008

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@article{Thomas2009PeptideconjugatedCP, title={Peptide-conjugated chlorin-type photosensitizer binds neuropilin-1 in vitro and in vivo.}, author={N. Thomas and Denise Bechet and Philippe Becuwe and Loraine Tirand and R{\'e}gis Vanderesse and Celine Frochot and François Guillemin and Muriel Barberi-Heyob}, journal={Journal of photochemistry and photobiology. B, Biology}, year={2009}, volume={96 2}, pages={101-8} }