title: Functionalization of the PEG Corona of Nanoparticles by Clip Photochemistry in Water: Application to the Grafting of RGD Ligands on PEGylated USPIO Imaging Agent.
abstract: The fast development of nanomedicines requires more and more reliable chemical tools in order to accurately design materials and control the surface properties of the nano-objects used in biomedical applications. In this study we describe a smooth and simple photografting technique, i.e., the clip photochemistry, that allows the introduction of molecules of interest in inert polymers or on stealth nanoparticles directly in aqueous solution. First we developed the methodology on polyethylene glycol (PEG) and looked for critical parameters of the process (irradiation times, concentrations, washings) by using several molecular probes and adapted analytical techniques ((19)F qNMR, EA, LSC). We found that the clip photochemistry in water is a robust and efficient method to functionalize PEG. Second we applied it on PEGylated USPIO (USPIO-PEG) magnetic resonance imaging agent and succeeded in introducing RGD peptide and homemade peptidomimetics on their PEG segments. The magnetic abilities of the conjugated nanoparticles were unchanged by the derivatization process as evidenced by their relaxometric properties and their NMRD profile. When tested on Jurkat lymphocyte T Cells, which express αvβ3 integrins, the USPIO conjugated with RGD ligands leads to an increase of the transverse relaxation rate (R2) by a factor 10 to 14 as compared to USPIO-PEG. Consequently, it makes them good candidates for targeted imaging technology in cancer therapy.
authors: ‡Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis Pasteur 1 bte L4.01.02, 1348 Louvain-La-Neuve, Belgium.
authors: Vincent
authors: V
authors: Pourcelle
authors: §Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, B-7000 Mons, Belgium.|#Center for Microscopy and Molecular Imaging (CMMI), Rue Adrienne Bolland, 8 B-6041 Gosselies, Belgium.
authors: Sophie
authors: S
authors: Laurent
authors: ‡Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis Pasteur 1 bte L4.01.02, 1348 Louvain-La-Neuve, Belgium.
authors: Alexandre
authors: A
authors: Welle
authors: ‡Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis Pasteur 1 bte L4.01.02, 1348 Louvain-La-Neuve, Belgium.
authors: Nicolas
authors: N
authors: Vriamont
authors: §Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, B-7000 Mons, Belgium.
authors: Dimitri
authors: D
authors: Stanicki
authors: §Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, B-7000 Mons, Belgium.|#Center for Microscopy and Molecular Imaging (CMMI), Rue Adrienne Bolland, 8 B-6041 Gosselies, Belgium.
authors: Luce
authors: L
authors: Vander Elst
authors: §Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, B-7000 Mons, Belgium.|#Center for Microscopy and Molecular Imaging (CMMI), Rue Adrienne Bolland, 8 B-6041 Gosselies, Belgium.
authors: Robert N
authors: RN
authors: Muller
authors: ‡Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis Pasteur 1 bte L4.01.02, 1348 Louvain-La-Neuve, Belgium.
authors: Jacqueline
authors: J
authors: Marchand-Brynaert
mesh_terms: D003287:Contrast Media / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D060328:Magnetic Phenomena; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D055668:Photochemical Processes; D011092:Polyethylene Glycols / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D008024:Ligands; D009842:Oligopeptides; D014867:Water; C000499:ferric oxide; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid