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Intensive program to develop anti-cancer vaccines based nanoscale particles
Scientists from the Laboratory of Glyconanotechnology at the CSIC in Seville, part of the UK-based Midatech Group, have initiated an intensive program to develop anti-cancer vaccines based upon creating immuno-stimulating nanoscale particles with an outer shell bearing specific carbohydrate and peptide antigens.
The team reports (1) (in Tetrahedron: Asymmetry) the successful synthesis of gold nanoparticles featuring covalently bonded, immunogenic oligosaccharides from the Ley determinant, which is associated with various carcinomas including colon, liver, prostate and ovarian.
The methodology ensures the preparation of functional, three-dimensional "glyco-stealth coronas" of immunogenic carbohydrate and peptide ligands on discreet, stable and water-soluble gold nanoparticles. To ensure maximum antigenicity, carbohydrate and peptide epitopes are linked covalently to the gold nanoparticle core by "spacers" of defined length. In this way a high surface density of the antigens is presented on the shell of the gold nanoparticles. Moreover these antigens are in their biologically correct conformation to stimulate antibody production.
The Lewis Y (LeY) determinant elicits antibodies against colon and liver carcinomas, and is over expressed in metastatic prostate cancer and in ovarian tumours. The LeY neoglycoconjugate synthesised consists of a tetrasaccharide covalently linked to a spacer (5 carbon chain) with a thiol end group. This is then covalently linked to the Au-S core.
The LeY-functionalised gold glyconanoparticles synthesized have been characterised by NMR spectroscopy and transmission electron microscopy (TEM). The particles are spherical in shape, with a mean diameter of 1.52 nm, from which it can be inferred that the cores contain 116-140 gold atoms.
Describing this important new development, Midatech Chief Operating Officer, Dr David Hill explains, "Of particular significance, is that the LeY-functionalised gold glyconanoparticles are very stable and water-soluble. In solution they are dispersed and discreet offering a highly immunogenic polyvalent system yet their microscopically minute dimensions of less than 2 nm means that the particles will be easily excreted by the kidneys.
The Midatech gold glyconanoparticles can be synthesized with specific carbohydrate and peptide moieties corresponding to well-characterised antigens from other cancer associated determinants, and we hope that this ingenious technology will lead to the creation of a range of novel, highly active anti-cancer vaccines in the future. Further studies are underway to evaluate the LeY-functionalised gold glyconanoparticles and Midatech will be announcing the results in due course."
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