Antibody-Functionalized Inorganic NPs: Mimicking Nature for Targeted Diagnosis and Therapy - Bioinspired Approaches for Human-Centric Technologies - page 8

range, is still challenging (Mader et al. 2010 ). Moreover, advances in synthetic
methods and optimization of the probe design led to the generation of dual imaging
nanosystems. Currently, in vivo studies are in progress to assess the potential of
these materials (Park et al. 2012 ; Zhou et al. 2010 ; Ju et al. 2012 ; Li et al. 2009 ).
In nanocrystals, apart from the intrinsic size dependence of the physical prop-
erties connected with the presence of an inorganic core, many other parameters,
individually or in combination, come into play in regulating their behavior when
applied to biological systems. Some of these parameters, in addition to size, are
shape, surface-to-volume ratio, and surface chemistry (Algar et al. 2011 ; Tao
et al. 2008 ; Pankhurst et al. 2003 ; Papavassiliou 1979 ; Alivisatos 1996 ; Whitesides
2003 ). It is important to emphasize that the size of the nanocrystals is in the same
range of that of many biomolecules, which permits the functionalization of their
surface with a controlled number of targeting molecules: these include peptides,
oligonucleotide sequences, proteins, vitamins, and others. In many cases, these
molecules can be bound to the nanocrystal surface in such a way that both the
number of molecules and their packing can be finely controlled, thus increasing the
affinity of the nanocrystals toward their target (Hauck et al. 2008 ; Nel et al. 2009 ).
This layer of organic/biomolecules bound to the surface of the nanocrystals can
affect their colloidal stability to different extents in the various biological fluids,
such as cellular media, serum, blood, gastric liquid, etc. Such layer can additionally
help the nanocrystals to preserve their intrinsic properties, depending on the
material of which they are made (fluorescence, superparamagnetism, plasmonic
behavior, etc.). One additional key role often played by this layer, when it is
sufficiently thick and robust, is that of minimizing the direct exposure of the
nanocrystal surface to the surrounding biological environment. This can clearly
reduce or even prevent the onset of adverse/side effects, for example, the leakage of
toxic (or potentially toxic) metal ions from the nanocrystals (Derfus et al. 2004 ; Nel
et al. 2006 ; Lewinski et al. 2008 ; Kirchner et al. 2005 ). Even more important, such
coating is capable of affecting the uptake of nanocrystals by the living cells,
especially if it is carefully designed for specific targeting of the cell. As an example,
when IONPs are used as hyperthermia agents or as carriers for the delivery of drugs,
nonspecific uptake needs to be avoided, so that the therapeutic effect is highly
specific and therefore side effects and toxicity to healthy tissues are reduced as
much as possible.
Specific targeting is of utmost importance for the identification of specific
cellular pathways, for instance, protein signaling or vitamin and hormone traffick-
ing toward different cellular sub-compartments. Engineered nanocrystals can also
be used for detecting and sorting of specific cell types within a biological sample.
For drug delivery applications, the use of antibodies could be exploited to direct the
nanocontainers toward the target tumor site which overexpresses specific antigen
against the antibody attached at the nanoparticle surface. The same principle is
exploitable for the delivery of nano-therapeutic tools (e.g., a plasmonic or a
magnetic nanoparticle) toward a tumor site or for in vivo imaging applications
using MRI.