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antigen-processing machinery. The dendritic cell-specific intercellular
adhesion molecule ICAM-3 grabbing non-integrin (DC-SIGN) and man-
nose receptor (MR) are C-type lectins expressed by DCs represent the
most frequently exploited glycan-functionalized nanosystems to promote
the process of antigen binding and uptake. As reported by van Kooyk
et al.,
12
the MR recognizes branch-end mono- and oligo-mannose resi-
dues, whereas DC-SIGN exhibits strong interactions with high-mannose
residues located more internally within a glycan structure. Additionally,
DC-SIGN contains a carbohydrate recognition domain that binds to
fucose-terminated glycan structures as well as Lewis-type blood antigens.
Within this context, a recent study proposed a strategy based on
liposomes modified with glycans for antigen targeting to DCs to boost
immune responses.
13
Glycoliposomes containing the antigen ovalbumin
(OVA) were prepared through the coupling of the glycans Lewis x (Le
x
)
and Lewis b (Le
b
) to both PEGylated and non-PEGylated liposomes. The
glycan modification used a post-functionalization of the liposomes based
on the conventional maleimide-lipid or maleimide-PEG-lipid coupling
technique, involving the thiol group of the glycans (Fig. 3). Following
this approach, the construction of the glycolipid backbones was achieved
in the final step of the process from commercial Mal-PEG(2000)-DSP
and MPB, introduced as lipid anchors in the bilayer during the
liposome preparation. Liposome binding to DC-sign was evaluated on
bone-marrow derived DC (BMDC) generated from DC-SIGN transgenic
and non-transgenic littermates. Surprisingly, the formulation was found
to have a strong impact on binding properties since PEGylation de-
creased the DC targeting eciency. The authors postulated that the
PEGylated liposomes
O
O
S
Glycan
Glycan
with SH
group
PEG
N
+
PEG
N
O
O
Liposome
Maleimide
Group
Targeted Liposome
Non-PEGylated liposomes
O
O
S
Glycan
Glycan
with SH
group
N
N
+
O
O
Liposome
Maleimide
Group
Targeted Liposome
Fig. 3 Reactions for conjugation of glycans on the maleimide group of PEGylated and
non-PEGylated liposomes.
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