Probing Cell-Surface Carbohydrate Binding Proteins with Dual-Modal Glycan-Conjugated Nanoparticles

Abstract

Dual-modal fluorescent magnetic glyconanoparticles have been prepared and shown to be powerful in probing lectins displayed on pathogenic and mammalian cell surfaces. Blood group H1- and Le(b)-conjugated nanoparticles were found to bind to BabA displaying Helicobacter pylori, and Le(a)- and Le(b)-modified nanoparticles are both recognized by and internalized into DC-SIGN and SIGN-R1 expressing mammalian cells via lectin-mediated endocytosis. In addition, glyconanoparticles block adhesion of H. pylori to mammalian cells, suggesting that they can serve as inhibitors of infection of host cells by this pathogen. It has been also shown that owing to their magnetic properties, glyconanoparticles are useful tools to enrich lectin expressing cells. The combined results indicate that dual-modal glyconanoparticles are biocompatible and that they can be employed in lectin-associated biological studies and biomedical applications.

Cell membrane-derived nanomaterials for biomedical applications

“…Used for biosensing, Lewis X has been conjugated onto fluorescent ferrite magnetic silica glyconanoparticles to probe mammalian and pathogenic cells in an attempt to understand the roles of specific surface lectins, and the platform also has further applications in diagnosing disease [94]. Recently, sialyl Lewis X, sialic acid, sialyllactose, sialyllactosamine and sulfated sialyllactoseamine were used to functionalize gold nanoparticles to develop a rapid diagnostic for distinguishing influenza strains [95].…”

Recent advances in biosensing using magnetic glyconanoparticles

“…Park et al [35] very recently reported the synthesis of fluorescent MNPs for the study of lectin-associated interactions in mammalian cells. Commercially available cobalt ferrite MNPs coated with a layer of silica containing rhodamine B isothiocyanate as a fluorescent probe were coupled to β-aminoethylated fucose-bearing oligosaccharides ( Fig.…”

“…These glycoMNPs were used as a magnetic resonance contrast agent for imaging poststroke endothelial inflammation in mice. In an elegant example of rational glyconanoparticle design, van Kasteren et al [38] used S-cyanomethyl as a Bmasked^functionality [19] with permission of the Royal Society of Chemistry; b Reprinted with permission from [35], copyright 2015 American Chemical Society) through the synthesis of oligosaccharides of increasing complexity, from monosaccharides to tetrasaccharides. In the last step of the assembly of the glycoconjugates, the Scyanomethyl moiety was activated to react with the amine groups present on the surface of amino-dextran-coated iron oxide nanoparticles.…”

“…More recently, Park et al [35] have developed dual-modal fluorescent glycoMNPs able to recognize mammalian and pathogenic cell surface lectins. Helicobacter pylori is an infectious pathogen that causes chronic gastritis, in which the adherence of H. pylori to the gastric mucosa plays an important role.…”

Glycan-based diagnostic devices: current progress, challenges and perspectives

“…Some TACAs, such as globo H and Le x , can be found within the blood-tissue group but do not normally appear on adult tissues, and are known as stage-specific embryonic antigens (SSEA). [41][42][43][44][45][46] Other examples include the detection of Helicobacter pylori by binding its BabA adhesion protein to Le a and Le b , 47 the detection of influenza virus and JC virus through sialoside binding to viral hemagglutinin and VP1 protein, respectively. 20 In addition to TACAs, secreted glycoproteins have also been used as biomarkers for cancer diagnosis.…”