Home
Project description
The aim is to explore the potential of gold Glyco-Nano-Particles (GNPs) as a probe for deepening the understanding of biomolecular interactions and as an instrument to solve biomedical problems. In particular, the innovative combination of a variable metallic core with specific homogenic or heterogenic ligands turns GNPs into vaccines and/or protective and directing vehicles to administer foodstuffs or drugs safely at their target location.
Biomolecular interactions and recognition underlie most life processes for normal functioning in growth, development and aging of cells as well as for disease related issues such as bacterial/viral infections or cancer. Controlled intervention in or manipulation of these interactions to combat diseases is at the basis of any regular treatment or prevention using medication or vaccination. The quality of the treatment depends on the selectivity and effectiveness of the active compound, and on the degree of selective delivery thereof at its target location.
This project is centred on functionalised GNPs that typically have a metallic core of gold covered with multiple spacered carbohydrate ligands. These particles can be tailor made to study and optimise the functioning of the active compound, to include special tags for diagnostic purposes, and to achieve targeted delivery. The project operates at the intersection of material science, nanosciences, and molecular biotechnology. This novel and highly interdisciplinary field of chemistry is closely associated with the physical and chemical properties of organic and inorganic nanoparticles, as well as with various aspects of organic/enzymatic synthesis, instrumental analytical techniques, computational chemistry and immunology. GNPs offer excellent, though challenging, opportunities to study biomolecular interactions and to explore some potential application areas.
Protein-protein and protein-DNA interactions are among the best known biomolecular interactions. They are relatively easy to study, because the interactions are generally strong. Carbohydrate-protein and carbohydrate-carbohydrate interactions, however, govern many crucial life processes, but are more difficult to study because the interactions are subtler, and multivalent exposure appears to be crucial for their real life function. The surfaces of most types of cells are covered with a dense coating of glycoconjugates (glycoproteins, proteoglycans and glycolipids), the glycocalix. Cellular adhesion and/or recognition are directed by selective attractive interactions involving these surface carbohydrates. Many diseases are caused by abnormalities in control mechanisms that affect the normal social behaviour of differentiated cells in multicellular organisms. Here the sugar chains of glycoconjugates come into play. They have a key function in the control of immunological and cellular functions, and in recognition processes between cells and their environments. Specific carbohydrate-protein interactions play a role in major human diseases like asthma, reperfusion damage (occurring e.g. in stroke and heart attack), rheumatoid arthritis or atherosclerosis and also in metastasis formation in some forms of cancer. Cell surface glycans are also connected with other important and potentially inhibits effects like bacterial infection, fertilisation and embryonic implantation as well as later developmental events, particularly angiogenesis.
Small molecules or glycoconjugates bearing a single carbohydrate epitope are rarely successful probes or interference vehicles in this environment. There is a need for versatile, inert molecules that allow a multivalent presentation of carbohydrate ligands. GNPs can be constructed to fulfil this need. Gold is an especially suitable inert carrier material, although other metals or semi-conductors can be used when needed to take advantage of their particular properties. Understanding underlying biomolecular interactions is required for the development of agonists or antagonists that can functionally intervene in the processes that cause disease. Improving health status is of great economic and social relevance.
The range of prospective applications of glyconanotechnology is immensely broad. It includes diagnostic kits, micro-arrays, glycomics, vaccines, anti-inflammatory drugs and targeted drug delivery agents against e.g. cancer, and bacterial or viral infections. GlycoGold will select several defined topics to explore.