title: Surface-engineered nanoparticles for multiple ligand coupling.
abstract: The design of surface-engineered nanoparticles for targeting to specific sites is a major challenge. To our knowledge, no study in the literature deals with ligand functionalization of biodegradable nanoparticles through biotin-avidin interactions. With the aim of conceiving small-sized nanoparticles which can be easily functionalized with a variety of ligands or mixtures thereof, biotinylated and PEGylated biotin-poly(ethylene glycol)-poly(epsilon-caprolactone) (B-PEG-PCL) copolymers were synthesized and used to prepare nanoparticles of around 100 nm. Avidin, followed by biotinylated wheat germ agglutinin as a model lectin, were coupled to their surface by taking advantage of the strong biotin-avidin complex formation. The cytotoxicity of the nanospheres towards Caco-2 cells in culture was negligible (more than 82% cell survival for nanoparticle concentrations up to 300 microg/well). The amount of radiolabeled poly(lactic acid) (PLA) or PEG-PLA nanoparticles associated with Caco-2 cells was only 0.7% and 1.5% of the amount added, respectively. This value was increased to 8.5% when a sufficient amount of lectin was bound to the PEG-PLA copolymer. After further studies, the biotin-PEG-coated nanoparticles could be helpful tools for studying the interaction between cells and functionalized nanoparticles with various surface characteristics (PEG layer density and thickness, ligand type and density).
authors.affiliation: School of Pharmacy, UMR CNRS, University of Paris Sud, 5 Rue J.B. Clément, Châtenay Malabry 8612, France. ruxandra.gref@cep.u-psud.fr
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Gillian
authors.initials: G
authors.lastname: Barratt
authors.forename: Evgueni
authors.initials: E
authors.lastname: Mysiakine
mesh_terms: D001665:Binding Sites; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D005027:Ethylene Oxide / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D013499:Surface Properties
chemical_list: D007202:Indicators and Reagents; D007783:Lactones; D008024:Ligands; C400421:PLC(20)-b-PEO(44); D005027:Ethylene Oxide