Biomedical Engineering Reference
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particle uptake by human CD34+, human CD4+ and mouse splenocytes (4-8 pg/cell)
compared to CLIO alone (<2 pg/cell) when labelled at 0.1 mg Fe/ml (Lewin et al.
2000
). However, the particles were located in the cell nucleus instead of the usual
endosomal location of other particles. This raises the question as to whether or
not CLIO-tat is more likely than other particles to alter cellular function through
interfering with nuclear activity. Instead of using peptides, it is possible to direct
receptor-mediated endocytosis with antibodies (Ab) as well. The transferrin receptor
is abundant on numerous cell types. Tagging SPIO with anti-transferrin Ab improved
the iron loading of human haemopoietic progenitor cells (9.8 pg/cell) over the
use of SPIO alone (2.4 pg/cell) (Daldrup-Link et al.
2003
). These particles were
internalised in contrast to another report where transferrin-coupled SPIO are only
bound to the surface of human dermal fibroblast (Berry et al.
2004
). Another anti-
body under exploration is CD11c, which increased SPIO uptake in dendritic cells
(Ahrens et al.
2003
).
An inherent problem with Ab-directed RME is the species-specific attachment
to the target receptor. This requires each Ab-SPIO to be tailored to the target species
and cell type. Moreover, from a clinical perspective, since Abs are typically deve-
loped in animals such as mice, this method will have to contend with regulations
on xenogeneic contamination of transplants. Finally, the production of antibodies
remains very expensive, and pharmacological doses required to obtain clinically useful
in vivo
labelling of cells would be prohibitive. For these reasons, it is expected that
such methods could only be used
in vitro
in the foreseeable future
.
4.3
Particle Size
As demonstrated in studies on a range of cell types, the rate and quantity of cellular
uptake of particles depends not only on particle composition but also on the particle
diameter. Early studies in macrophages showed that the volume of particles taken
up increased in tandem with increasing particle diameter, with maximal uptake
reached at around 2 mm (Pratten and Lloyd
1986
; Tabata and Ikada
1988
). As
diameters increased from 2 to 4.6 mm, the volume of particles taken up actually
decreased. This may not be surprising if we consider that the larger of such particles
approach the size of whole cells. . It was also shown that leukocytes took up more
styrene-based particles of diameter 500 nm-1 mm than particles of other sizes
(Kawaguchi et al.
1986
). A similar result was shown where both macrophages
(Zhang et al.
2001
) and monocytes (Metz et al.
2004
) took up greater masses of
60 nm carboxydextran-coated SPIO than similarly coated but smaller USPIOs.
There have been only a few studies of non-phagocytic cells on how particle
size affects uptake. When labelled with carboxydextran-coated particles between
17 and 65 nm, lung carcinoma cells take up greater masses of the larger particles
(Matuszewski et al.
2005
). Non-phagocytic cells tend to show maximum uptake at
a lower size range compared to macrophages. Rejman et al demonstrated that uptake
into murine melanoma cells decreased as polystyrene particles diameter increased
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