Biomedical Engineering Reference
In-Depth Information
The polymer coating around iron oxide particles provides repulsive forces between
particles in the form of electrostatic repulsion or steric hindrance to enable stable
suspension in water. Clinically-available SPIO such as ferumoxide or ferucarbotran
are well suspended in water due to the steric hindrance offered by their dextran or
dextran-derivative coating (Hunter
1995
).
Various particle coatings have been engineered to enhance or avoid specific
particle-cellular interactions (Nath et al.
2004
). Both macromolecules and monomers
have been used as coating material. An example of macromolecular coating is the
'PEGylation' of iron oxide to allow for a long circulation time by avoiding opsoni-
sation and uptake by the macrophages of the reticuloendothelial system (Lee et al.
2006
). The PEGylated surface is hydrophilic, electrostatically neutral and without
hydrogen donor or acceptors, which explains the lack of attractive forces between
PEG and opsonising proteins.
Particles that are stabilised by monomer coating remain suspended due to the
electrostatic repulsion between particles. Charge polarity can also affect particle
uptake by cells. Positively and negatively-charged particles with diameters similar
to SPIO (100 nm) were compared in terms of uptake by Hela cells (Harush-Frenkel
et al.
2007
). The anionic polylactide-based particles provide poorer uptake than
their aminated, cationic cousins. It was shown that the cationic particles used the
clathrin- and caveolae-mediated endocytic pathways, but not the anionic ones.
Interestingly, when the clathrin/caveolae pathway was inhibited, Hela cells took up
the cationic particle through a possibly compensatory, macropinocytic pathway.
Such data suggests that at least some cell types have more than one mechanism by
which they can be labelled with various iron particles, and that the mechanism used
may vary depending on the labelling conditions and the particle composition.
In addition to charge polarity, the zeta potential, an indication of particle
surface with respect to bulk medium, plays an important role in the efficiency of
particle uptake by cells. Citrate-coated VSOP (8 nm) showed improved uptake
by macrophages compared to uncharged particles of similar size (Fleige et al.
2002
). Supporting this observation, anionic dimercaptosuccinic acid-coated AMNP
(−30 mV in zeta potential) showed greater uptake by macrophages and Hela cells
compared to dextran-coated ferumoxtran (of similar size) which carries no charge
(Wilhelm et al.
2003
; Jung
1995
). Comparison of zeta potentials between iron
oxide particles is difficult due to the indirect determination of zeta potential from
electrokinetic techniques, a process highly dependent on the approximation of
particle rigidity (as a result of different coatings) (Di Marco et al.
2007
). Further
comparison of particles with similar sizes and coatings but differing zeta potentials
is required to understand the effect of particle charge on labelling efficiency.
4.2
Surface Ligand
Another method to improve cellular uptake is to encourage receptor-mediated
endocytosis (RME) using biological ligands. Attachment of HIV tat peptide to
aminated, dextran-cross-linked iron oxide particles (CLIO-tat, ~45 nm) improved
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