Review
Glyconanoparticles: Types, synthesis and applications in glycoscience, biomedicine and material science

https://doi.org/10.1016/j.bbagen.2005.12.001Get rights and content

Abstract

Nanoparticles are the subject of numerous papers and reports and are full of promises for electronic, optical, magnetic and biomedical applications. Although metallic nanoparticles have been functionalized with peptides, proteins and DNA during the last 20 years, carbohydrates have not been used with this purpose until 2001. Since the first synthesis of gold nanoparticles functionalized with carbohydrates (glyconanoparticles) was reported, the number of published articles has considerably increased. This article reviews progress in the development of nanoparticles functionalized with biological relevant oligosaccharides. The glyconanoparticles constitute a good bio-mimetic model of carbohydrate presentation at the cell surface, and maybe, excellent tools for Glycobiology, Biomedicine and Material Science investigations.

Introduction

During the last 20 years, there has been a great deal of interest in the self-assembly fabrication of hybrid materials from inorganic nanoparticles and biomolecules [1]. As nanoparticles and biomolecules are of a similar length scale (Fig. 1), it seems logical that the combination of biomacromolecules to nanomaterials can provide interesting tools for mimicking the biomolecules which are present at cellular systems, probing the mechanisms of biological processes, as well as developing chemical means by handling and manipulating biological components [2]. At present, it is straightforward to control and modify the properties of nanostructures to better suit their integration with biological systems; for example, controlling their size, modifying their surface layer for enhanced aqueous solubility, biocompatibility, or biorecognition [2], [3], [4]. The use of gold nanoparticles in biological applications was first highlighted in the 1970s with the immunogold staining procedures [5]. Since then, the labeling of target molecules with gold nanoparticles has revolutionized the visualization of cellular and/or tissue components by electron microscopy. During the last 10 years, several groups have prepared gold nanoparticles functionalized with proteins and DNA [1]. These nanoparticles are being used for assembling new materials, developing bioassays and as multivalent systems for interaction studies.

Although several reviews on nanomaterials functionalized with proteins, peptides, DNA and RNA have been published in the last decade [1], [2], [6], [7], [8], [9], [10], [11], as far as we know, only one of them has been partially reported on nanoparticles covered with carbohydrates (glyconanoparticles) [12]. For this reason, the main aim of this manuscript is the review of the synthetic methods and applications of these new hybrid materials made of inorganic nanoparticles and biologically relevant oligosaccharides.

Carbohydrates are, together with nucleic acids and proteins, important molecules for life. Much is already known about the structure, interactions and function of nucleic acids and proteins, however, the role of carbohydrates in the cell is less clear. The surface of mammalian cells is covered by a dense coating of carbohydrates named glycocalyx [13]. In the glycocalyx, carbohydrates appear mainly conjugated to proteins and lipids (glycoproteins, glycolipids and proteoglycans) and it is as glycoconjugates that they develop their biological function. Now, it is known that these complex oligosaccharides are involved in the control of many normal and pathological processes [14], [15].

A characteristic feature of the biological interactions where carbohydrates are involved is their extreme low affinity that has to be compensated by multivalent presentation of the ligands. For this reason, we developed a new integrated approach based on the use of nanoparticles that we have named the Glyconanotechnology strategy [12] to study and evaluate carbohydrate–carbohydrate and carbohydrate–protein interactions. After our first manuscript on the application of gold glyconanoparticles to study the self-aggregation of Lex trisaccharide in the presence of calcium appeared in 2001 [16], several research groups have developed different strategies to prepare and apply nanoparticles functionalized with biologically relevant oligosaccharides to study carbohydrate interactions or to intervene in carbohydrate-mediated biological processes. After 5 years, there are enough results to state that carbohydrates are joining proteins, peptides and DNA as biological partners of inorganic nanomaterials to intervene in biological processes (Fig. 2).

Although numerous examples of gold and magnetic nanoparticles protected and stabilized with polysaccharides as chitosan or dextran have appeared in the literature [17], [18], [19], [20], [21], [22], this review is focused on nanoparticles functionalized with biologically relevant oligosaccharides, where the oligosaccharides confer biological functionality to the inorganic core of the nanomaterial rather than playing a simple stabilizing role.

Section snippets

Types and synthesis of glyconanoparticles

Three different types of nanoparticles functionalized with oligosaccharides have been reported so far: gold and silver glyconanoparticles, semiconductor glyco-quantum dots and magnetic glyconanoparticles.

Application of glyconanoparticles

The glyconanoparticles constitute a good bio-mimetic model of carbohydrate presentation at the cell surface, opening new avenues in the field of chemical Glycobiology [12] and Biomedicine (Fig. 6). In spite of the short history of these new glyconanomaterials, some applications have already been reported, focused mainly on the study and evaluation of carbohydrate interactions. Furthermore, few reports have appeared on glyconanoparticles as biolabels or biosensors and some applications in

Conclusions and perspectives

In this review, we have presented methods to prepare, in an easy way, a variety of water-soluble and stable glyconanoparticles. All these nanomaterials are good biomimetic models of carbohydrate presentation at the cell surface.

As mentioned above, the main application of these new multivalent systems is the study of carbohydrate-mediated interactions opening new avenues in Glycobiology. Though the simple and flexible preparation of these glyconanoclusters and their interesting physical,

Acknowledgements

We thank the colleagues in the Carbohydrate Group who have decisively contributed to the glyconanoparticles development. They are cited in the corresponding references. We thank also Prof. M. Martin-Lomas for his support and fruitful discussions. This work was supported by MEC (Grant BQU2002-03734) and CSIC (I3P contract).

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