Biomedical Engineering Reference
In-Depth Information
cationic density, which can compromise the membrane's integrity and lead to
cytotoxicity.
As with protein interactions, surface charge, particle size, hydrophobicity, and
surface roughness play an important role in particles' interactions with
phospholipids. It is known that hydrophobic particles tend to agglomerate and are
quickly removed by the reticuloendothelium. Moreover, nanoscale surface rough-
ness significantly decreases repulsive interactions, thus promoting adhesion on NPs
to lipid membranes and easing their endocytosis.
1.4.2 Biological Response to Nanomaterials
Despite intensive in vitro research on the interaction of nanomaterials with
biological compounds, very little is known about the in vivo fate of nanoparticles.
Current knowledge is based on few studies addressing the endocytic pathways of
small quantities of fluorescent or radiolabelled nanomaterials. In order to determine
the in vivo impact of nanomaterials, it is primordial to study the cellular responses
relative to the physicochemical properties of the nanoparticles used. This section
will explore the internalization and uptake process of nanoparticles, as well as their
potential cytotoxic effect.
1.4.2.1
Internalization and Uptake
Nanoparticles cause an extensive array of intracellular responses contingent on
their physicochemical properties, concentrations, time of contact, subcellular
distributions, and interactions with biological molecules.
The human body recognizes all nanoparticles as foreign entities; therefore, they
are quickly removed from the blood circulation [
84
]. Multiple in vitro and in vivo
studies dealing with mechanisms of NP uptake in different cell types and NP
distribution in animal models demonstrate that there is not one common uptake
mechanism for NP. Endocytosis is the process by which cells absorb material from
outside the cell. Endocytic pathways comprise pinocytosis, the formation of
caveolae and clathrin, and caveolae/clathrin-independent uptake. Phagocytosis is
the process by which cells ingest particles as they are sealed off into a large vacuole
known as a phagosome. Phagosomes fuse with lysosomes in their maturation
process, forming phagolysosomes. Pinocytosis is the biological process of the cell
membrane to form a pocket (vesicle). The filling of the vesicle occurs in a
nonspecific manner. The vesicle then travels into the cytosol and fuses with other
vesicles such as endosomes and lysosomes. Caveolae consist of internalization of
particles by the protein caveolin-1 with a bilayer enriched in cholesterol and
glycolipids. Caveolae are pits in the membrane that resemble the shape of a cave.
Clathrin-mediated endocytosis is the uptake facilitated by membrane localized
receptors and ion channels. These receptors are associated with the cytosolic
