Carbohydrate-Coated Fluorescent Silica Nanoparticles as Probes for the Galactose/3-Sulfogalactose Carbohydrate–Carbohydrate Interaction Using Model Systems and Cellular Binding Studies

The carbohydrates galactose and 3-sulfogalactose, found on sphingolipids in myelin, interact with each other via a carbohydrate-carbohydrate interaction (CCI). In oligodendrocytes, this interaction triggers a signaling cascade resulting in cytoskeletal rearrangements and reorganization of glycolipids and proteins at the cellular surface. These rearrangements can also be triggered by synthetic multivalent glycoconjugates. In this report, we describe the synthesis of glycan-coated silica nanoparticles and their subsequent binding to cultured oligodendrocytes and purified myelin. Fluorescent silica nanoparticles with an azidosiloxane-derived outer shell were functionalized with carbohydrates using the copper-promoted azide-alkyne cycloaddition reaction. The carbohydrate-carbohydrate interaction between galactose and 3-sulfogalactose was examined by measuring the binding of 3-sulfogalactose-containing nanoparticles to galactolipids that had been immobilized in a multiwell plate. Particle aggregation mediated by CCI was observed by TEM. The interaction of the particles with oligodendrocytes and purified myelin was examined using fluorescence microscopy, providing direct evidence for binding of galactose and 3-sulfogalactose-coated nanoparticles to oligodendrocytes and myelin fragments.