Peptide-conjugated chlorin-type photosensitizer binds neuropilin-1 in vitro
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- 作者：Noé ; mie Thomas ; Denise Bechet ; Philippe Becuwe ; Loraine Tir ; Ré ; gis V ; eresse ; Cé ; line Frochot ; Franç ; ois Guillemin ; Muriel Barberi-Heyob
- 关键词：Targeted phototherapy ; Vascular effect ; Neuropilin-1 ; siRNA ; Peptide ; Glioma-bearing nude mice
- 刊名：Journal of Photochemistry and Photobiology B: Biology
- 出版年：2009
- 出版时间：3 August 2009
- 年：2009
- 卷：96
- 期：2
- 页码：101-108
- 全文大小：1364 K
文摘
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.