Surface-engineered nanoparticles for multiple ligand coupling

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 mug/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). (C) 2003 Elsevier Ltd. All rights reserved.