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

Paper ID Volume ID Publish Year Pages File Format Full-Text
30347 44471 2009 8 PDF Available
Title
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.

Keywords
Targeted phototherapy; Vascular effect; Neuropilin-1; siRNA; Peptide; Glioma-bearing nude mice
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Peptide-conjugated chlorin-type photosensitizer binds neuropilin-1 in vitro and in vivo
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 96, Issue 2, 3 August 2009, Pages 101–108
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us