Biomedical Engineering Reference
In-Depth Information
Thus, the particles remain in the circulatory system and have better chances to
reach their target. Uncoated nanoparticles are less efficiently internalized
because of their tendency to agglomerate into large aggregates that are less
endocytosed. This could be the result of interactions with the proteins or the salt
of the physiological media that would reduce repulsive interactions between par-
ticles. Among the polymer-coated particles, PEI-coated nanoparticles (PEI = poly-
ethyleneimine) are easily solubilised in physiological conditions and do not
form large aggregates, probably due to the high charge density obtained with the
coating (Fuller et al.
2008
).
4.2
Improving Nanoparticles Uptake
Cellular uptake of silica-based nanoparticles is governed by parameters such as cell
line, morphology of the particles, electrostatic interactions between cellular mem-
brane and nanoparticles, surface functionalization of the particles. The mechanism
of internalization depends on these parameters that can be tuned to favour one
pathway upon the others.
4.2.1
Influence of Morphology (Size and Shape)
In order to develop intracellular drug delivery system, the morphology of the nano-
particles should be controlled to optimize the extent of internalization depending on
the aim of the system. Different studies show that, as a general trend, spherical
particles are more easily internalized than rod-shape or tubular particles, but this
depends on the cell-line considered (Trewyn et al.
2008
) (Fig.
8
). One hypothesis
to explain such a difference is the so-called “wrapping time” parameter. Indeed, if
the particles are internalized through endocytosis, a membrane must be formed
around the particle before the uptake process can take place and wrapping a tubular
shape is slower than for a spherical shape. But this has to be moderated taking into
account the aspect ratio of the particles. Indeed, short rods seem to be as easily
internalized as spherical nanoparticles. Another point not to miss is that apart from
the influence on the uptake efficiency, the morphology of the nanoparticles and
more particularly their aspect ratio can strongly influence the cell cytoskeleton and
the viability (Huang et al.
2010
). Indeed some studies have proven that rod-shape
silica particles, once internalized, have an effect on the F-actin network as well as
a critical impact on cytotoxicity (by enhancing apoptosis). Size is also a critical
parameter because it will strongly influence the type of pathway followed for the
internalization. Silica nanoparticles can be obtained with a size varying from a few
nanometers to hundreds of nanometers, depending on the synthesis chosen.
Generally, particles smaller than 200 nm will be preferentially internalized through
endocytosis, particles bigger than 200 nm will either be endocytosed or not
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