Wrong Resemblance? Role of the Immune System in the Biocompatibility of Nanostructured Materials - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 298

in enhancing the immune response to several antigens [61]. These
properties certainly call for investigations addressing whether
lipid formulations applied for making drug-carrying liposome may
influence the function of the immune system.
Several coatings that suppress or reduce the immune response
have been developed. Notably polyethylene glycol (PEG) is efficient
in increasing the circulation time of nanoparticles apparently due to
significant reduction of these particles in activating the complement
system [43, 62, 63]. Even so, a recent report points to that certain
mechanisms involving ficolins and complement factors of the lectin
pathway may activate complement by ficolin binding to PEG [64,
65]. Furthermore, antibodies may also recognize PEG pointing to
the importance of repeated injection of PEG in experimental animal
models to evaluate antibody formation.

10.3.2 Size, Shape, and the Immune Response

The size of nanoparticles and other nanomaterials is a factor in
determining the immune response. This is not surprising when
considering that particles with diameters of 20-200 nm take
dimensions similar to many viruses and debris from the growth of
larger microorganisms such as yeasts and bacteria. The immune
system comprises many mechanisms for handling such material,
which complicates evasion.
The physiological importance of the size of nanomaterials,
e.g., nanoparticles, has mainly been emphasized in relation to the
penetration of particles into the tissue through leaky vessels or
in cellular uptake [66]. Receptor-mediated uptake of particulate
material by macrophages is possible for particles larger than
approximately 50 nm. Smaller particles are also found intracellularly,
but the uptake is likely to depend on spontaneous mechanisms
such as pinocytosis. The distinction between receptor-mediated
particle uptake and other routes of uptake is significant since the
ligation of receptors on the leukocyte cell surface, e.g., β 2 integrins,
supports the synthesis of cytokines such as TNF- α . Consequently,
as demonstrated by several studies in the area of environmental
medicine, particle size may have a role in determining the immune
response [67] although a simple relation between particle size and
immune response is not likely to exist. As discussed by others [68],
particle size is not necessarily a well-defined property due to the