Antibody-Functionalized Inorganic NPs: Mimicking Nature for Targeted Diagnosis and Therapy - Bioinspired Approaches for Human-Centric Technologies - page 9

In all these cases, the main goal is to achieve specific targeting while minimizing
at the same time nonspecific targeting. Properly designed conjugates/nanocrystals
have been fabricated to combine the novel and fascinating properties and potential
of nanoscale materials (i.e., colorimetric signature, fluorescence, plasmonic behav-
ior, and unique features deriving from nanoscale magnetism) with biomolecules
such as whole antibodies or fragments of them. This was made possible by the high
versatility of the chemistry at the nanoparticle surface and by the efforts undertaken
by different groups to overcome the critical issues related to the preparation of the
desired antibody-nanoparticle formulations. The surface chemistry functionali-
zation of inorganic nanoparticles is a key issue in this respect, and it will be
discussed in the next paragraph.
1.4 Surface Functionalization of Inorganic Nanoparticles
Inorganic nanoparticles can be synthesized following different routes. Among the
many approaches, non-hydrolytic methods (for instance, thermal decomposition of
organometallic precursors in hot surfactants) or hydrolytic methods, like water-
based reduction or coprecipitation, are perhaps the most suitable ones for the
preparation of high-quality colloidal nanoparticles (Sun et al. 2004 ; Murray
et al. 1993 ; Brust et al. 1994 ). Using these methods, the particles are usually coated
by a layer of stabilizers: if the nanoparticles are synthesized by thermal decompo-
sition methods, then the coating usually consists of organic surfactant molecules,
whereas if the particles are synthesized in water, the coating can be represented by
charged salt counterions or charged surfactants. The coating in general is weakly
bound to the nanoparticle surface and can be easily replaced with other types of
agents, depending on the further use that one wants to make of the particles
(Neuberger et al. 2005 ; Hezinger et al. 2008 ; Chithrani and Chan 2007 ). In the
case of nanoparticles synthesized in organic media, new ligand molecules, mono-
or multidentate, might confer to the nanoparticle a different solubility from one
phase to another, thus allowing the transfer from the solvent in which they have
been synthesized to the aqueous media. In the case of nanoparticle prepared directly
in water, ligand molecules with proper moieties that can bind the nanoparticle
surface with higher affinity than the original capping molecules can be chosen. This
leads to a better stabilization of the nanoparticles in water.
The ligand molecules could be also chosen to introduce at the nanoparticle
surface specific functional groups needed for further functionalization with differ-
ent molecules, including antibodies, antibody fragments, or peptides.
Usually, the exchanged ligands are short molecules, and upon the replacement of
the original surfactant molecules at the nanoparticle surface, the final size of the
nanocrystals is comparable to that of the initial ones. It is important to remark that a
small particle size and the surface charge (together with other parameters) affect the
cell internalization pathway, as proven by different groups (Nel et al. 2009 ;
Delehanty et al. 2009 ). In most cases, the binding of the ligand to the particle