Dendritic Groups on Nanomaterial Surfaces
A R T I C L E S
have been used to target nanoparticles,17-19 and micelles20,21
to tumors expressing elevated levels of the Rvꢀ3 integrins.
Small-molecule targeting groups are also particularly attrac-
tive due to their ease of preparation and simple conjugation
chemistry. Folic acid, a small molecule, has been extensively
used for targeting dendritic polymers,22,23 micelles,24,25 and
nanoparticles26,27 to tumors expressing elevated levels of the
folic acid receptor. Carbohydrates such as mannose and glucose
have been demonstrated to provide enhanced delivery into
macrophages28,29 and bacteria.30-32 Although small molecules
often possess only moderate binding affinities for their biological
targets, the incorporation of multiple copies of these molecules
onto nanomaterial surfaces can provide multivalent systems
which exhibit significantly enhanced binding.33 On the other
hand, some binding affinity may be lost through steric inhibition
by polymer chains, which are present at the surface of most of
these materials, and this effect has not yet been investigated in
detail. In addition, the density and spatial distribution of ligands
on the surfaces can also play a role. Thus, the goal of this work
was to investigate whether the way in which biological ligands
are displayed at the surfaces of polymer assemblies and
nanoparticles affects their binding to biological targets.
As illustrated in Figure 1, it was anticipated that the
introduction of ligands to surfaces using a dendritic approach
would provide enhanced availability of the ligands, in com-
parison with individual small molecules conjugated without a
dendritic scaffold, which may become easily buried within a
polymer layer at the surface. For this study, mannose was
selected as a model biological ligand, as its multivalent binding
to targets such as Concanavalin A (Con A) has been extensively
investigated and a number of assays have been developed to
evaluate this binding.34-38 Dendritic displays of mannose have
been previously demonstrated by several groups to provide
Figure 1. Schematic comparison of a surface functionalized with (a)
nondendritic versus (b) dendritic groups.
enhanced binding to Con A in comparison with monovalent
mannose,39-41 but their effect on the presentation of mannose
at polymeric surfaces has not been investigated. Here, the effect
of dendritic versus nondendritic surface functionalization was
investigated using polymer vesicles formed from poly(butadiene-
block-ethylene oxide) (PBD-PEO) and dextran-coated iron oxide
nanoparticles as model materials. The results described here are
expected to be generalizable to a wide variety of materials, thus
providing a framework for enhancing targeting efficiency for a
wide range of biomedical applications.
Results and Discussion
Preparation of Polymer Vesicles Functionalized with
Dendritic Mannose. Polymer vesicles are among the classes of
polymer assemblies that have received significant attention in
recent years.42-46 The availability of both hydrophobic and
hydrophilic compartments, as well as their increased strength
and stability relative to their phospholipid vesicle analogues
(liposomes), have made them attractive materials for recent
applications in imaging and drug delivery.47-53 Thus, they are
ideal materials for the exploration of surface functionalization
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