Biomedical Engineering Reference
In-Depth Information
ability of certain types of particles to aggregate in the presence of
biomacromolecules, e.g., albumin. These problems can be dodged
by appropriate modifications of the particle surface. Using a layer
of PEG, Larsen et al. recently demonstrated that smaller rather than
larger USPIO accumulated tumors in an experimental model. The
accumulation involves macrophages in the tumor tissue. As expected,
smaller particles with a diameter of 20 nm were less efficiently
phagocytosed than larger particles with a diameter of 40 nm [43].
While the influence of particle size on phagocytosis is well
established, a surprising role of particle shape was uncovered by
Champion and Mitragoti [69]. The comparisons were made with
particles with distinct geometric shapes, including spheres, oblate
ellipsoids, prolate ellipsoids, elliptical disks, rectangular disks, and
“UFOs” with appropriate variation in sizes, thickness and aspect
ratios. All particles were opsonized by an IgG-coating. Obloid objects
were more readily phagocytosed than spherical or UFO-like objects.
By contrast, the volume of the particles did not seem to aff ect the
phagocytosis as prominently as shape. Supported by microscopical
analyses, Champion and Mitragoti suggested that actin polymerization
in the phagocyte play a role in the shape dependence of phagocytosis
[69]. Interestingly, there is evidence that phagocytosis of naturally
occurring targets for the immune system such as certain bacteria
also is a process where oblate bacteria cells are ingested in a non-
random fashion with regard to the ultrastructure of the uptake [69].
Although the biology of this phenomenon is poorly understood, it
encourages a speculation that the shape sensitivity of phagocytosis
serves some purpose in elimination of bacteria.
The regulation of the immune response by target surface topology
is not restricted to processes involving phagocytosis. Pedersen
et al. recently reported that complement activation by dextran-
coated nanoparticles depended on the diameter of the particles in
such a way that larger particles (with a diameter of 600 nm) failed
activation, while smaller particles (with a diameter of 250 nm)
strongly activated complement [70]. The activation was initiated by
the classical pathway and comparison of the responses from donors
identified IgM antibodies to dextran as playing a major role in the
complement activation. In solution, IgM is a planar molecule [4]. It
was previously suggested that this conformation does not permit
binding of the C1 complex and hence complement activation, while
the surface-bound molecule in a “staple”-like conformation exposes
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