RESUMEN
There is a need for biofunctionalised magnetic nanoparticles for many biomedical applications, including MRI contrast agents that have a range of surface properties and functional groups. A library of eleven adducts, each formed by condensing a reducing sugar with a catechol hydrazide, for nanoparticle functionalisation has been created using a high-throughput chemical synthesis methodology. The enzymatic transformation of an N-acetylglucosamine (GlcNAc) adduct into an N-acetyllactosamine adduct by ß-1,4-galactosyltransferase illustrates how chemoenzymatic methods could provide adducts bearing complex and expensive glycans. Superparamagnetic iron oxide nanoparticles (8 nm diameter, characterised by TEM, DLS and SQUID) were coated with these adducts and the magnetic resonance imaging (MRI) properties of GlcNAc-labelled nanoparticles were determined. This straightforward approach can produce a range of MRI contrast agents with a variety of biofunctionalised surfaces.
RESUMEN
A simple synthetic route has been devised for the production of coating agents that can give multivalent displays of saccharides on the surface of magnetite nanoparticles and phospholipid vesicles. A versatile and potentially high-throughput condensation reaction allowed the rapid synthesis of a variety of glycosylhydrazide conjugates with lipid, resorcinol or catechol termini, each in good yield and high anomeric purity. The hydrolytic stability of these adducts was assessed in D2O at different pD values using (1)H-NMR spectroscopy, whilst quartz crystal microbalance with dissipation monitoring (QCM-D) confirmed that the saccharide functionality on bilayers and on nanoparticles was still available to lectins. These multivalent saccharide displays promoted nanoparticle interactions with cells, for example N-acetylglucosamine-coated nanoparticles interacted much more effectively with 3T3 fibroblasts than uncoated nanoparticles with these cells. Despite potential sensitivity to oxidation, catechol coatings on magnetite nanoparticles were found to be more stable and generate better nanoparticle interactions with fibroblasts than resorcinol coatings.
