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presence of such PEG
2000
chains may alter mobility and proper orien-
tation of the glycans hampering interaction with DC-SIGN.
The use of the non-PEGylated liposomes coated with Le
b
or Le
x
ligands
was further investigated to examine DC-SIGN-specific internalization by
murine and human DCs as well as the effect of the glycan functionali-
zation on antigen-presentation.
14
The data clearly indicated that the
coating of liposomes with DC-SIGN-binding glycans resulted in increased
binding and uptake through DC-SIGN. More importantly, in the presence
of lipopolysaccharides (LPS), these nanosystems decorated with glycans
led to 100-fold more e
cient presentation of the encapsulated antigens
to CD4
þ
and CD8
þ
T-cells compared to unmodified liposomes or sol-
uble antigens.
In the same way, mannosylated liposomes were developed to enhance
the uptake of liposomal formulations by DCs and the subsequent DCs
activation through an ecient mannose receptor (MR)-mediated endo-
cytosis. Over the last few years, major attention has been directed towards
the impact of ligand multivalency and clustering effects on mannose
residues-MR binding strength. Indeed, knowledge of the optimal degree
of ligand mannosylation is a crucial parameter for determining the op-
timal mannose density on the liposomal surface for ecient cellular
recognition and internalization. For that purpose, Frisch et al.
15,16
syn-
thesized mono-, di-, and tetra-antennary mannosyl lipid structures in
which the mannosyl headgroups were linked via a polyethylene spacer to
a 1,2-dioleyl-sn-glycero-diether as the lipid moiety (Fig. 4).
These glycolipids were easily and stably incorporated into the bilayer of
unilamellar
liposomes
consisting
of
phosphatidylcholine/
OH
OH
O
H
HO
O
A
O
O
O
S
N
H
O
O
O
OH
O
H
O
H
HO
O
OH
S
O
O
H
O
H
O
B
HO
HO
O
S
O
O
O
H
HN
O
O
O
O
O
O
OH
O
H
O
H
HO
O
OH
O
H
S
O
O
H
O
H
HO
O
S
O
O
O
N
H
O
C
HN
O
O
O
N
H
O
O
OH
O
H
O
O
HO
HO
HN
O
O
OH
OH
S
O
O
N
H
O
H
HO
O
S
O
O
N
H
Fig. 4 A: Man
1
DOG; B:Man
2
DOG; C: Man
4
DOG.
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