Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload.

Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVβ3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cytotoxic payload in a novel design. usGNPs were synthesized with a modified Brust-Schiffrin method and functionalized via amide coupling and ligand exchange and their uptake, intracellular trafficking, and toxicity were characterized.

DM1 Loaded Ultrasmall Gold Nanoparticles Display Significant Efficacy and Improved Tolerability in Murine Models of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with poor prognosis and limited options for treatment. Life expectancy after diagnosis is short; the currently available treatments are not well tolerated and have limited clinical benefit. There is a clear unmet clinical need for the development of new treatments.

Modulating glycosidase degradation and lectin recognition of gold glyconanoparticles.

Glyconanoparticles (GNPs) are water-soluble carbohydrate-functionalized gold nanoclusters with a promising potential to serve as versatile tools in studies ranging from basic chemical glycobiology to clinical applications. In this paper we evaluate the influence of ligand density and presentation on the recognition by protein receptors by examining the interaction of lactose-functionalized GNPs with two different galactose-specific carbohydrate-binding proteins: an enzyme, Escherichia coli beta-galactosidase, and a lectin, Viscum album agglutinin. The results suggest that the proper selection of ligand densities and spacers in GNP functionalization is an important requisite to match the topological requirements of the target receptor while escaping glycosidase degradation.

Preparation of multifunctional glyconanoparticles as a platform for potential carbohydrate-based anticancer vaccines.

A novel platform for anticancer vaccines has been prepared using glyconanotechnology recently developed in our laboratory. Ten different multifunctional gold glyconanoparticles incorporating sialylTn and Lewis(y) antigens, T-cell helper peptides (TT) and glucose in well defined average proportions and with differing density have been synthesised in one step and characterised using NMR and TEM. Size and nature of the linker were crucial to control kinetics of S-Au bond formation and to achieve the desired ligand ratio on the gold clusters.

Thermodynamic evidence for Ca2+-mediated self-aggregation of Lewis X gold glyconanoparticles. A model for cell adhesion via carbohydrate-carbohydrate interaction.

Thermodynamic evidence for the selective Ca(2+)-mediated self-aggregation via carbohydrate-carbohydrate interactions of gold glyconanoparticles functionalized with the disaccharides lactose (lacto-Au) and maltose (malto-Au), or the biologically relevant trisaccharide Lewis X (Le(X)-Au), was obtained by isothermal titration calorimetry. The aggregation process was also directly visualized by atomic force microscopy. It was shown in the case of the trisaccharide Lewis X that the Ca(2+)-mediated aggregation is a slow process that takes place with a decrease in enthalpy of 160 +/- 30 kcal mol(-)(1), while the heat evolved in the case of lactose and maltose glyconanoparticles was very low and thermal equilibrium was quickly achieved.

Gold glyconanoparticles as new tools in antiadhesive therapy.

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.

Gold glyconanoparticles: synthetic polyvalent ligands mimicking glycocalyx-like surfaces as tools for glycobiological studies.

A simple and versatile methodology is described for tailoring sugar-functionalised gold nanoclusters (glyconanoparticles) that have 3D polyvalent carbohydrate display and globular shapes. This methodology allows the preparation of glyconanoparticles with biologically significant oligosaccharides as well as with differing carbohydrate density. Fluorescent glyconanoparticles have been also prepared for labelling cells in biological tests.

Gold Glyconanoparticles as Water-Soluble Polyvalent Models To Study Carbohydrate Interactions.

Glycosphingolipid clustering and interactions at the cell membrane can be modeled by gold glyconanoparticles prepared with biologically significant oligosaccharides. Such water-soluble gold glyconanoparticles with highly polyvalent carbohydrate displays (see picture, gray hemisphere: gold nanoparticle) have been obtained by a simple and versatile strategy.