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Abstract:
First preparation of carbohydrate conjugate nanoparticles used as specific luminescent Glyco-quantum dots with potential roles in in-vivo and in-vitro cellular imaging

New Glyconanoparticle Study shows potential

May 02, 2005

Scientists from the Carbohydrate Group of Glyconanotechnology in Seville have reported (in Tetrahedron: Asymmetry) an ingenious glyconanoparticle-based approach to developing bioactive fluorescence probes for specifically labelling carbohydrate cell receptors. Using a novel single-step solution procedure to synthesize the carbohydrate nanoparticles, the Group have overcome the numerous problems related to coupling biomolecules to semiconductor Quantum dots. Ultimately, the UK-based Midatech Group of Companies behind this new technique aims to create water soluble, stable and biologically active Quantum dots for use in in-vivo and in-vitro screening and therapeutic techniques (1).

Semiconductor nanoparticles of nanosized dimensions (Quantum dots) can provide powerful fluorescence probes which emit light at a variety of precise wavelengths with the exact colour mainly dependent on the dot size. Importantly, these Quantum dots are 100 times more photo-stable than organic dyes and often reveal a long fluorescence lifetime. Up until now however, the preparation of Quantum dots conjugated to carbohydrate antigens for specific cell targeting has not been possible.

The study authors, Professors Jesús M de la Fuente and Soledad Penadés report the first successful production of stable, water-soluble glyco-Quantum dots (glyco-QDs) as potential bio-conjugates for in-vitro and in-vivo cellular imaging. These glyco-Quantum dots consist of Cadmium-Sulphur cores which are powerful fluorescent probes emitting light at a variety of precise wavelengths depending on the dot size, surrounded by a covalently attached shell of specific carbohydrate chains. These glyco-QDs present the carbohydrate antigens in a three-dimensional and polyvalent array conferring biological specificity. As such they provide a customisable tool for visualising and investigating the antigens involved in cellular adhesion and potentially other biological phenomena.

In this paper, glyco-QDs have been created with the disaccharide, maltose and the tri-saccharide antigen Lewis X (Le^x) as tools for targeting specific cell sites. Analysed by transmission electron microscopy, the glyco-QDs are discreet, dispersed nanoparticles, spherical in shape, of a diameter between 2 and 5 nm.

The Lewis X (Le^x) antigen is involved in aggregation of teratocarcinoma cells and morula compaction - in embryology this is the transitional 32-cell phase during which the spherical blastomere flattens and differentiation of the embryo begins. The Le^x - QDs are now being used as polyvalent, luminescent tools to observe aggregation of F9 teratocarcinoma cells, with the malto-QDs as a control system.

David Hill, Chief Operating Officer of Midatech, the recently formed biopharmaceutical company set-up to promote the unique work of the Carbohydrate Group in Seville explains, "It is now well known that specific carbohydrates located on cell walls play important antigenic roles. They also confer biological differentiation and are involved with inter-cellular interactions such as cellular adhesion. As such there is considerable potential application for water-soluble, nano-scale particles with specific carbohydrate "shells" which have the ability to mimic the glycoshingolipid presentation at the cell surface.

David continues, "Midatech is developing these glyconanoparticles with the aim of creating specific probes for diagnostic purposes, and also to develop carriers for therapeutic agents destined for particular cells. We have found a unique and simple method by which we can create self-associating, water soluble, heterogeneous synthetic nanoparticles and nanocells. We expect that our nanocells will have an unlimited number of applications in medicine."

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All the above-mentioned scientific papers are available on CD - please contact the Healthcare Solutions Press Office for a copy. Please note that the CD is Adobe Acrobat software compatible.

Notes to Editors:
The Carbohydrate Group in Seville established in 2002 (2) 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 company formed in 2004 based on the patent-protected technology platform developed 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.

References:

Glyco-quantum dots: a new luminescent system with multivalent carbohydrate display. JM de la Fuente, S Penadés. Tetrahedron: Asymmetry 16 (2005) 387-391
Gold Glyconanoparticles as Building Blocks for Nanomaterials Design. TC Rojas, JM de la Fuente et al. Advanced Materials 2002, 14, No.8 April 18, 585-588

Media Contact:
Sarah Rogers
Healthcare Solutions
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Hyde Lane, Churt, FARNHAM, Surrey, GU10 2LP
UK Tel: ++(0)1428 604444
sarah@healthcare-pr.co.uk

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