June 21, 2005 --- 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 (Le Y ) determinant elicits antibodies against colon and liver
carcinomas, and is over expressed in metastatic prostate cancer and in ovarian
tumours. The Le Y 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 Le Y -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 Le Y -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 Le Y -functionalised
gold glyconanoparticles and Midatech will be announcing the results in due
course."
Reference:
Synthesis of a Le Y neoglycoconjugate and Le Y -functionalized gold glyconanoparticles.
JL de Paz et al. Tetrahedron: Asymmetry 16 (2005) 149-158
Notes :
The Carbohydrate Group in Seville established in 2001 that
new well-defined, water soluble, three-dimensional carbohydrate polyvalent models
or "nanocells" could
be synthesised in the form of gold glyconanoparticles as a means to study biologically
valuable carbohydrate interactions. These "nanocells" reproduce the clustering
of cell-attached receptors and they can be considered as a useful tool for the
rational analysis of carbohydrate interactions and as tools for the development
of new techniques for screening diagnosis and therapy.
Midatech Ltd is the UK-based company formed in 2004 to develop the patent-protected
technology platform generated by the Carbohydrate Group to focus on potential
applications for gold glyconanoparticles in four key areas: imaging, drug delivery,
siRNAs and DNA and vaccines - both therapeutic and preventative.
Contact:
Sarah Rogers
Healthcare Solutions
Hyde Lodge, Hyde Lane, Churt, FARNHAM, Surrey, GU10 2LP, UK
Tel: ++(0)1428 604444
sarah@healthcare-pr.co.uk
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