Biomedical Engineering Reference
In-Depth Information
and opening the pore. Thus such systems enable a control of the release and no
premature release. Coupled to a targeting moiety, such device could be used for
specific and controlled drug delivery.
4.3.2
Targeted Delivery (Cellular and Intracellular)
One of main issues in biomedical sciences nowadays is to develop drug delivery
systems that can be specifically targeted to the desired site. These systems are
mainly based on recognition with binding receptor of the targeted cells. Different
chemical structures can be grafted to silica nanoparticles to obtain these selective
interactions, as for example antibodies, peptides or specific ligands. The use of folate
groups has been mentioned previously. Such ligands are useful to target cancer cells
that possess folate-receptors in larger numbers than healthy cells (Rosenholm et al.
2009
). Experiments on porous hybrid silica nanoparticles, functionalized with PEI
and folic acid have shown that the number of particles internalized per cell is signifi-
cantly larger in cells expressing high levels of folate receptors, as well as the propor-
tion of cells that have internalized particles (Fig.
10
). Furthermore, this kind of
functionalized silica particles have proven to have a specific targeting capacity with
no cytotoxicity detected. Folic acid is grafted via carbodiimide/ succinimide
coupling of the carboxylic acid group of folic acid with the amine groups on the
surface of the PEI-coated particles, in a buffer at acidic pH. However, one limitation
appears in using folate-targeted particles that is the low rate of escape of the vector
after receptor-mediated endocytose (Breunig et al.
2008
). Using these biomolecule
conjugations with functionalized silica particles, different antibodies (e.g. monoclonal
antibodies) or peptides can be grafted to target specific cells. Cellular targeting is
extensively studied
in vitro
and different ways have been developed but yet there are
very few reports of
in vivo
testing (Lu et al.
2010
).
Apart from cellular targeting, intracellular targeting can also be considered with
delivery of the drug to a specific organelle. Once the particles have escaped the endo-
some, they can either remain into the cytosol or diffuse specifically towards mito-
chondria or nucleus depending on the action site aimed for the drug. The nucleus is
a major subcellular structure and has to be targeted for gene delivery. To answer this
issue, mesoporous silica nanoparticles have been successfully combine with a den-
drimer assembly that act as gatekeeper for the gene transfection system trapped in
the pores (Radu et al.
2004
). The dendrimer (generation two of poly(amidoamine))
was grafted on an isocyanatopropyl functionalised particle and efficiently bind plas-
mid DNA vectors. Furthermore, this hybrid material is able to protect DNA against
enzymatic cleavage and induce expression of the DNA vector in the targeted cells.
4.4
Intracellular Fate of the Nanoparticles
While conceiving silica-based drug delivery system, the fate of the internalized
particles must be evaluated. There are three possibilities: the particles can be degraded
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