Chemistry Reference
In-Depth Information
Glycolipid-based nanosystems for the
delivery of drugs, genes and vaccine
adjuvant applications
Thierry Benvegnu,*
a,b
Lo
ยจ
c Lemi
`
gre,
a,b
Caroline Ballet,
a,b
Yvan Portier
a,b
and Daniel Plusquellec*
a,b
DOI: 10.1039/9781849739986-00341
The application of nanotechnology for cellular delivery of drugs, macromolecules and
DNA therapeutics, clearly offers new opportunities in the treatment of the major health
threats including cancer, infections, metabolic diseases, autoimmune diseases, and in-
flammations. The main challenge of today's nanotechnology is probably to develop sys-
tems that allow real progress to achieve high protection of the active ingredient and spatial
site-specific delivery. Glycolipids are amphiphilic molecules that could fulfill these con-
ditions by improving the physical properties of the nanocarriers and facilitating cell/tissue
specific targeting through carbohydrate-cell protein interactions. Glycolipids designed for
this purpose should, however, possess some general features allowing specific and high
a
nity with the targeted cells as well as easy incorporation into the drug carriers. The aim
of this chapter is to present the most recent accomplishments in the field of nanosystems
containing glycolipids as drug/gene delivery systems and adjuvants for vaccine appli-
cations, with a special attention to the role of the carbohydrate moieties in these novel
nanotherapeutic strategies.
1 Introduction
Glycolipids are amphiphilic compounds containing one or more mono-
saccharide residues bonded by a glycosidic linkage to a hydrophobic
moiety such as an acylglycerol, a sphingoid, a ceramide (N-acylsphingoid)
or a prenyl phosphate. In addition to glycoproteins, proteoglycans and
glycosaminoglycans, glycolipids constitute the glyco-components that lie
on the exterior (extracellular) surfaces of the cells. This carbohydrate-rich
layer, known as a glycocalyx, plays an important role in mediating cell-
specific interactions and preventing nonspecific protein adsorption.
1
The
possible diversity of the carbohydrate chain in glycolipids, and more
generally in glycoconjugates, is quite important: it can vary by the
number of sugars (from mono- to oligosaccharides), by the linear or
branched structure of the chain and by the sequence of the particular
sugars. The heterogeneity and specificity in these oligosaccharide struc-
tures can be decoded by several carbohydrate-recognizing proteins, called
lectins, that act as primordial mediators in recognition phenomena in-
volving cells and proteins. In particular, C-type lectins comprise a large
family of receptors found in all organisms that bind to carbohydrates
in a calcium-dependent manner.
2
They include collectins, selectins,
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