caa a22 4500 445312149 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s11095-011-0398-5 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0398-5 "Click” Conjugation of Peptide on the Surface of Polymeric Nanoparticles for Targeting Tumor Angiogenesis [Elektronische Daten] [Stéphanie Deshayes, Victor Maurizot, Marie-Claude Clochard, Cécile Baudin, Thomas Berthelot, Stéphane Esnouf, Didier Lairez, Michel Moenner, Gérard Déléris] ABSTRACT: 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 fluorescence 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 fourdays 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. Springer Science+Business Media, LLC, 2011 angiogenesis nationallicence "click” chemistry nationallicence cyclo-peptide nationallicence nanoparticles nationallicence PVDF nationallicence tumor targeting nationallicence AA : acrylic acid nationallicence ACN : acetonitrile nationallicence DCM : dichloromethane nationallicence DIEA : diisopropylethylamine nationallicence DLS : dynamic light scattering nationallicence DMEM : Dulbecco's modified eagle medium nationallicence EDC : ethyl-3(3dimethylaminopropyl)carbodiimide nationallicence EDTA : ethylenediaminetetraacetic acid nationallicence EGM-2 : endothelial growth medium nationallicence ESI : electrospray ionization nationallicence FBS : fetal bovine serum nationallicence FESEM : field emission scanning electron microscope nationallicence FTIR : fourier transform infrared nationallicence HCMEC : human brain endothelial cells nationallicence HOBt : N-hydroxybenzotriazole nationallicence HPLC : high-performance liquid chromatography nationallicence HUVEC : human umbilical vein endothelial cells nationallicence IC50 : half-maximal inhibitory concentration nationallicence Ip : polydispersity index nationallicence MALDI-TOF : matrix-assisted laser desorption/ionization-time of flight nationallicence mTEG : modified tetraethyleneglycol nationallicence NIR : near-infrared nationallicence NMP : N-methylpyrrolidone nationallicence NMR : nuclear magnetic resonance nationallicence PAA : poly(acrylic acid) nationallicence PAE : porcine aortic endothelial cells nationallicence PBS : phosphate-buffered saline nationallicence POA : perfluorooctanoic acid nationallicence PVDF : poly(vinylidene fluoride) nationallicence Rg : radius of gyration nationallicence Rh : hydrodynamic radius nationallicence SANS : small-angle neutron scattering nationallicence SLS : static light scattering nationallicence t -BuOH : tertio-butanol nationallicence TFA : trifluoroactic acid nationallicence THF : tetrahydrofurane nationallicence TIS : triisopropylsilane nationallicence UV : ultra-violet nationallicence VEGF : vascular endothelial growth factor nationallicence VEGFR : receptor of VEGF nationallicence VF2 : vinylidene fluoride nationallicence WST-1 : 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate nationallicence XPS : X-ray photoelectron spectroscopy nationallicence Deshayes Stéphanie CNAB, Chimie Bio-Organique, UMR CNRS 5084, Université de Bordeaux 2, 33076, Bordeaux, France aut Maurizot Victor CNAB, Chimie Bio-Organique, UMR CNRS 5084, Université de Bordeaux 2, 33076, Bordeaux, France aut Clochard Marie-Claude Laboratoire des Solides Irradiés, UMR CNRS-CEA 7642 Ecole Polytechnique, 28 route de Saclay, 91128, Palaiseau, France aut Baudin Cécile Laboratoire des Solides Irradiés, UMR CNRS-CEA 7642 Ecole Polytechnique, 28 route de Saclay, 91128, Palaiseau, France aut Berthelot Thomas Laboratoire des Solides Irradiés, UMR CNRS-CEA 7642 Ecole Polytechnique, 28 route de Saclay, 91128, Palaiseau, France aut Esnouf Stéphane Laboratoire de Radiolyse, Service de Chimie Moléculaire, UMR CNRS-CEA 3299, 91191, Gif-Sur-Yvette, France aut Lairez Didier Laboratoire Léon Brillouin, UMR CNRS-CEA 12, 91191, Gif-Sur-Yvette, France aut Moenner Michel Laboratoire des Mécanismes Moléculaires de l'Angiogenèse, INSERM U920 Université de Bordeaux 1, 33405, Talence, France aut Déléris Gérard CNAB, Chimie Bio-Organique, UMR CNRS 5084, Université de Bordeaux 2, 33076, Bordeaux, France aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1631-1642 0724-8741 28:7<1631 2011 28 11095 https://doi.org/10.1007/s11095-011-0398-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0398-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Deshayes Stéphanie CNAB, Chimie Bio-Organique, UMR CNRS 5084, Université de Bordeaux 2, 33076, Bordeaux, France aut NATIONALLICENCE 700 1- Maurizot Victor CNAB, Chimie Bio-Organique, UMR CNRS 5084, Université de Bordeaux 2, 33076, Bordeaux, France aut NATIONALLICENCE 700 1- Clochard Marie-Claude Laboratoire des Solides Irradiés, UMR CNRS-CEA 7642 Ecole Polytechnique, 28 route de Saclay, 91128, Palaiseau, France aut NATIONALLICENCE 700 1- Baudin Cécile Laboratoire des Solides Irradiés, UMR CNRS-CEA 7642 Ecole Polytechnique, 28 route de Saclay, 91128, Palaiseau, France aut NATIONALLICENCE 700 1- Berthelot Thomas Laboratoire des Solides Irradiés, UMR CNRS-CEA 7642 Ecole Polytechnique, 28 route de Saclay, 91128, Palaiseau, France aut NATIONALLICENCE 700 1- Esnouf Stéphane Laboratoire de Radiolyse, Service de Chimie Moléculaire, UMR CNRS-CEA 3299, 91191, Gif-Sur-Yvette, France aut NATIONALLICENCE 700 1- Lairez Didier Laboratoire Léon Brillouin, UMR CNRS-CEA 12, 91191, Gif-Sur-Yvette, France aut NATIONALLICENCE 700 1- Moenner Michel Laboratoire des Mécanismes Moléculaires de l'Angiogenèse, INSERM U920 Université de Bordeaux 1, 33405, Talence, France aut NATIONALLICENCE 700 1- Déléris Gérard CNAB, Chimie Bio-Organique, UMR CNRS 5084, Université de Bordeaux 2, 33076, Bordeaux, France aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1631-1642 0724-8741 28:7<1631 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer