Biomedical Engineering Reference
In-Depth Information
protein clathrin, which initiates the formation of a vesicle by forming a crystalline
coat on the inner surface of the cell's membrane.
As other factors, the importance of uptake depends on the physicochemical
properties of the NP such as chemical composition, size, geometry, surface charge,
coating, aggregation status, the exposed cells, and their microenvironment. Particle
size and shape are believed to be key parameters for endocytotic pathways. Particle
sizes of less than 120 nm are believed to adhere to endocytic uptake; however, little
existent scientific data confirms this notion. While limited studies imply a correla-
tion between particle size and endocytic mechanisms, most lack appropriate nano-
particle characterization and rely on nonspecific inhibitors to hinder endocytic
uptake. Uptake mechanisms of NP in specific cells of the immune system like
neutrophils, monocytes, macrophages, and dendritic cells have been studied by
several investigators, and it is well known that macrophages are predominantly
involved in these mechanisms [
82
]. Phagocytosis uptake mechanisms are believed
to favor particles bigger than 500 nm. However, nanomaterials can agglomerate and
are therefore capable of being phagocytosed. The scientific literature is incongruent
with regard to the relationship between the sizes of primary nanoparticles, aggre-
gation, agglomeration, and their phagocytotic potential. Obvious discrepancies in
the literature corroborate the fact that our understanding of such systems is limited.
The surface modification of nanoparticles is an important issue in terms of the
control of internalization and their uptake by cells and targeted tissue. For instance,
binding of transferrin ligands to its receptors triggers endocytosis through clathrin-
coated pits. The abundance of caveolae in mammalian cells impacts their potential
for caveolae-mediated endocytosis. This type of uptake appears to play as an
important role entry mechanism for viruses into cells. It is thus believed that
caveolar entry and transport into cells can be favored by adopting viral coat
proteins.
Lastly, the protein corona greatly impacts the fate of the nanoparticle in a
biological environment. Albumin, immunoglobulins, complement, fibrinogen, and
apolipoproteins tend to bind more strongly to nanomaterials and have been shown
to promote opsonization, phagocytosis, and endocytosis.
1.5 Cytotoxicity
Cytotoxicity can be analyzed by different features [
85
]. In the literature, various
studies state that the exposition of NPs to cells can affect the cellular, subcellular,
and genetic behavior and induce cell's death through disruption of the plasma
membrane's integrity, mitochondrial damage, and impairment of the nucleus.
Exposure of the body to nanoparticles is believed to trigger an inflammatory
response and provoke oxidative stress that will ultimately lead to cell death.
Cytokine production and disturbance of the oxidant and antioxidant cellular pro-
cesses are believed to be key factors in NP cytotoxicity.
