Silica-Based Nanoparticles for Intracellular Drug Delivery - Intracellular Delivery: Fundamentals and Applications - page 345

3.2 Surface Modification of Silica Particles

As mentioned earlier, proper surface modification of silica nanoparticles can
improve their drug delivery capability and efficiency. This can be performed by
chemical binding or physical adsorption. A typical modifier is an antibody molecule
decorating a carboxyl-functionalized silica nanoparticle. In that case, the carboxyl
groups on the silica surface form amide bonds with the primary amine groups of
antibodies. The immobilized antibody can then more effectively direct the nanopar-
ticle toward a specific tissue or cell type. Another example of the chemical binding
approach to immobilize recognition elements is the formation of disulfide bonds.
However, the electrostatic forces that govern the physical adsorption of biocompatible
macromolecules are often the most simple and efficient method for immobilization.
Many macromolecules, such as PEG, proteins or lipids can be physically adsorbed
onto nanoparticles surface to decorate them with a variety of functional groups
(Van Shooneveld et al. 2008 ; Thierry et al. 2008 ).
Despite dye-doped silica nanoparticles can be linked to biorecognition elements
such as antibodies or DNA molecules via physical adsorption onto the surface par-
ticle, covalent attachment of such molecules is preferred, not only to avoid desorp-
tion from the particle surface, but also to get a better control of the biorecognition
function localization. So, an alternative way relies on the stable incorporation of
imaging or therapeutic agents via covalent bonding using trialkoxysilane-derived
molecules that contain suitable organic moieties. These molecules can be incorpo-
rated into the silica matrix through silanol linkages during particle synthesis, leading
to stable hybrid material with uniform agents throughout the nanoparticle that are
protected from the environment. The silica nanoparticles can also be post-synthetically
modified by reacting with the trialkoxysilane precursor. This post-synthesis grafting
is particularly useful for modifying the particle surface with selected agents that are
not stable during the silica particle synthesis. During the post-coating step, the
particle surface first needs to be modified with suitable functional groups such as
thiol, amine or carboxyl groups.
For the Stöber nanoparticle synthesis, surface modification is usually done after
nanoparticle synthesis to avoid potential secondary nucleation, but co-condensation
is also possible: through the use of respective organosilane, organic functionalities
such as alkyl, thiol, amino, cyano/isocyano, vinyl/alkyl, organophosphine or aromatic
groups can be incorporated into the pore walls of the silica network. Surface modi-
fication of microemulsion nanoparticles can be achieved in the same manner or via
direct hydrolysis and co-condensation of TEOS and other organosilanes present in
the microemulsion solution (Deng et al. 2000 ). This method allows a multi-step
sequence procedure, very useful for imaging or therapeutic cargoes incorporation.
After attachment of the desired functionality to the silica nanoparticle, further modi-
fications can be undertaken, through the additional functional group, by the way of
conjugation chemistry. For instance, an amine-modified particle can be reacted with
various carboxylate-containing molecules to form a stable amide bond. During con-
jugation with biomolecules, the colloidal stability of the nanoparticles in solution