Gold Glyconanoparticles as New Tools in Antiadhesive Therapy

Abstract

Gold glyconanoparticles (GNPs) have been prepared as new multivalent tools that mimic glycosphingolipids on the cell surface. GNPs are highly soluble under physiological conditions, stable against enzymatic degradation and nontoxic. Thereby GNPs open up a novel promising multivalent platform for biological applications. It has recently been demonstrated that specific tumor-associated carbohydrate antigens (glycosphingolipids and glycoproteins) are involved in the initial step of tumor spreading. A mouse melanoma model was selected to test glyconanoparticles as possible inhibitors of experimental lung metastasis. A carbohydrate-carbohydrate interaction is proposed as the first recognition step for this process. Glyconanoparticles presenting lactose (lacto-GNPs) have been used successfully to significantly reduce the progression of experimental metastasis. This result shows for the first time a clear biological effect of lacto-GNPs, demonstrating the potential application of this glyconanotechnology in biological processes.

Epidermal growth factor receptor tyrosine kinase is modulated by GM3 interaction with N-linked GlcNAc termini of the receptor

“…The present study addresses a specific type of N-glycosylation of the receptor, its role in receptor interaction with microenvironmental GM3, and how GM3 and Nglycosylation cooperatively regulate EGFR function. A few previous lines of investigation indicate that GM3 interacts with various carbohydrates, such as those with GalNAc␤ 1-4Gal␤ 1-4Glc (14-17), with Gal␤ 1-4Glc (18,19), with lactosylsphingosine (20), or with N-linked glycan having multivalent GlcNAc termini (21). We therefore studied the correlation between GM3 interaction and EGFR-associated N-linked glycan.…”

Multivalent display of oligosaccharides on nanoparticles accelerates their nuclear import

“…C. The studies of sugar-dependent nuclear import using nanoparticles For the further study of sugar-dependent nuclear import, we proposed an approach that used nanoparticles as a scaŠold. Penades et al demonstrated that sugar-sugar interactions, which are di‹cult to detect due to their weak binding force, could be clearly detected using sugardisplaying gold nanoparticles (21)(22)(23)(24). As demonstrated in associated studies, sugar-displaying nanoparticles aŠord an eŠective tool for the production of molecular-binding forces based on the multivalent interaction of carbohydrates.…”

Synthesis of Neu5Ac-Gal-functionalized gold glyconanoparticles

“…2,3 Gold nanoclusters functionalized with carbohydrates provide a well-defined chemical composition to intervene in the cell-cell adhesion and recognition processes where carbohydrates are involved. [4][5][6][7][8] However, assembly of glyconanoparticles from authentic oligosaccharides are rather difficult due to the insufficient quantities and methodology limitations, while the syntheses of these oligosaccharides are complex and often feature low overall yields. 9 The mission may be considerably simplified if target structures are represented by pseudo-oligosaccharides or oligosaccharide mimics in which certain glycosidic bonds are substituted with non-glycosidic motifs.…”