“Click” Conjugation of Peptide on the Surface of Polymeric Nanoparticles for Targeting Tumor Angiogenesis - Laboratoire des Solides Irradiés (LSI) Accéder directement au contenu
Article Dans Une Revue Pharmaceutical Research Année : 2011

“Click” Conjugation of Peptide on the Surface of Polymeric Nanoparticles for Targeting Tumor Angiogenesis

Résumé

Purpose Angiogenesis plays a critical role in tumor growth. This phenomena is regulated by numerous mediators such as vascular endothelial growth factor (VEGF). CBO-P11, a cyclo-peptide, has proven to specifically bind to receptors of VEGF and may be used as targeting ligand for tumor angiogenesis. We herein report the design of novel nanoparticles conjugated to CBO-P11 in order to specifically target tumor site. Methods The conjugation of CBO-P11 on the surface of poly (vinylidene fluoride) (PVDF) nanoparticles was investigated using the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition known as " click " reaction. CBO-P11 was modified with a near-infrared cyanine dye bearing an alkyne function, allowing both " click " coupling on azido-modified nanoparticles and fluores-cence labelling. Each step of this nanodevice construction was judiciously performed in aqueous solution and successfully characterized. The cytotoxicity of nanoparticles was evaluated in human brain endothelial cell line and their affinity for VEGF receptors was determined via fluorescence-based uptake assays on porcine aortic endothelial cell line. Results Nanoparticles were found to be spherical, dense, monodisperse and stable. No cytotoxicity was observed after four days of incubation, demonstrating the biocompatibility of nanoparticles. Fluorescence highlighted the specific interaction of these functionalized nanoparticles for VEGF receptors, suggesting that the targeting peptide bioactivity was retained. Conclusions These results demonstrate the potential of these functionalized nanoparticles for targeting tumor angiogenesis and their possible use as multifunctional plateform for cancer treament if coupled with therapeutic agents. KEY WORDS angiogenesis. " click " chemistry. cyclo-peptide. nanoparticles. PVDF. tumor targeting ABBREVIATIONS AA acrylic acid ACN acetonitrile DCM dichloromethane DIEA diisopropylethylamine DLS dynamic light scattering DMEM Dulbecco's modified eagle medium EDC ethyl-3(3dimethylaminopropyl)carbodiimide EDTA ethylenediaminetetraacetic acid EGM-2 endothelial growth medium ESI electrospray ionization FBS fetal bovine serum Electronic supplementary material The online version of this article (doi:10.1007/s11095-011-0398-5) contains supplementary material, which is available to authorized users.

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hal-01129046 , version 1 (12-03-2015)

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Stéphanie Deshayes, Victor Maurizot, Marie-Claude Clochard, Cécile Baudin, Thomas Berthelot, et al.. “Click” Conjugation of Peptide on the Surface of Polymeric Nanoparticles for Targeting Tumor Angiogenesis. Pharmaceutical Research, 2011, pp.1631. ⟨10.1007/s11095-011-0398-5⟩. ⟨hal-01129046⟩
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