Silica-Based Nanoparticles for Intracellular Drug Delivery - Intracellular Delivery: Fundamentals and Applications - page 339

in physico-chemical conditions occurs, especially higher temperature (37°C) and
ionic strength (ca. 0.1 M). As mentioned above, this leads to a higher solubility
that is reached by a fast dissolution reaction. But the most important parameter is
the silica concentration, which is typically below 1 mg/mL (0.015 M). As a com-
parison, the solubility of silica in these conditions is ca. 0.1 mg/mL so that the
relative fraction of soluble silica becomes significant. Indeed, higher ionic strength
can also induce nanoparticle aggregation. However, biological media also contain
a considerable amount of proteins that will adsorb either unspecifically or specifi-
cally (during opsonization) (Lord et al 2006 ). The surface of silica nanoparticles
being negatively charged, the first process will take place for positively-charged
proteins and the second is very likely to occur as it is know to be specifically effective
for anionic surface. As mentioned earlier, this adsorption will tend to decrease the
rate of solubilization (Finnie et al. 2009 ).
An increase in porosity, especially in the case of mesoporous particles, can have
two effects (Bass et al 2007 ; Lu et al. 2010 ; Izquierdo-Barba et al. 2010 ) First,
because of higher specific surface area the dissolution rate will be increased when
compared to plain particles. Secondly, because pores are present on the surface, less
surface silanol groups are present. As a consequence, the surface charge is decreased,
that should favor particle aggregation in purely inorganic media. In parallel, it may
also decrease the available sites for protein binding in biological fluids. Indeed,
every procedure that leads to a modification of particle surface will modify its
behavior in solution. In many cases, long chain hydrophilic groups have been
grafted to limit opsonization phenomena (Cauda et al. 2010 ). At the same time,
because this procedure also decreases the density of surface silanol groups, it
should also decrease particle solubility, as indicated earlier. Accordingly, homoge-
neous nanocomposite particles exhibit different properties from plain silica colloids
because the (bio)-organic component is also present on the particle surface. In par-
ticular, their solubility depends strongly on the solubility of the additive. For
instance, the dissolution of alginate/silica particles has been studied both in solution
and within cells, showing that the biopolymer solubilization occurs before that of
silica, leading to a rearrangement of the particle internal structure (Yang and
Coradin 2008 ; Boissière et al. 2006 ).

2.3.2 In Vitro Interactions with Cells

The toxicity of silica-based materials has been studied for a very long time, but
most of the studies were related to asbestos fiber-induced silicosis in lungs tissues
(Bagchi 1992 ). As early as the 60's, it was found that silica particles could interfere
with the integrity of biological membranes, probably by interaction between the
negatively-charged surface and the positively-charged groups of proteins or phos-
pholipids (Depasse 1977 ). Further studies demonstrate that silica particles could
impact on alveolar macrophages that produce specific proteins triggering fibroblast
proliferation and therefore formation of fibrous tissues (Arcangeli et al. 1990 ).
It was also suggested that not only the particle surface but also its solubilization