volume ratio and offer the opportunity to modify this surface with different molecules. For example, targeting ligands such as aptamers can be used for nanoparticle
modification [5]. Important aspects of aptamer coupling to nanoparticles are
highlighted in the section below.
This chapter deals with the application of aptamer-modified nanoparticles with a
focus on both therapeutic (Sect. 3) and diagnostic (Sect. 2) applications.
1.1 Coupling of Aptamers to Nanoparticles
Aptamers can either be immobilized to nanoparticles by covalent coupling or in a
non-covalent way [6–9]. Most immobilization strategies require a site-specific
modification of the aptamer; these modifications are commonly introduced during
the aptamer synthesis [10]. Covalent coupling can, e.g., be performed via
carbodiimide coupling chemistry [6]. Non-covalent coupling can be performed by
utilizing affinity ligands (e.g., streptavidin and biotin) [9]; physisorption, e.g.,
between thiol-modified aptamers and gold nanoparticles [7]; or π-stacking between
nucleotide bases of the aptamer and the side walls of single-walled carbon nanotubes
(SWNTs) [8].
To ensure the functionality of nanoparticle-coupled aptamers, some parameters
have to be considered. Aptamers depend on their three-dimensional structure for
target recognition and binding; disrupting the native structure of an aptamer may
lead to a loss of affinity [11]. Therefore the density of immobilized aptamers must be
optimized carefully. Too high densities can result in non-correct folding of aptamers
[12], while too low aptamer density can reduce the binding capacity of the
functionalized nanoparticle. Furthermore the surface charge of the nanoparticle can
affect aptamer folding, e.g., a positive-charged surface can interact electrostatically
with the negative-charged aptamers and lead to aptamer unfolding. In some cases
aptamers that are bound directly to a surface cannot adapt their correct folding
because of their proximity to the surface; in these cases spacers (e.g., poly T spacers)
can be used to increase the distance of the aptamers to the surface and therefore allow
correct folding. The orientation of aptamer immobilization can also affect aptamer
functionality; in this case both 3
0 and 5
0 terminal modifications should be investigated to optimize functionality of the aptamer orientation [13].
If these aspects are taken into account, aptamer-modified nanoparticles can be a
promising tool for medical applications including diagnostics and therapy.
1.2 Aptamer-Modified Nanoparticles and Multivalent
Binding
Nanoparticles hold the potential to carry more than one aptamer, thereby facilitating
multivalent binding with dramatically increased affinity. Here either several copies
Aptamer-Modified Nanoparticles in Medical Applications
163
modification [5]. Important aspects of aptamer coupling to nanoparticles are
highlighted in the section below.
This chapter deals with the application of aptamer-modified nanoparticles with a
focus on both therapeutic (Sect. 3) and diagnostic (Sect. 2) applications.
1.1 Coupling of Aptamers to Nanoparticles
Aptamers can either be immobilized to nanoparticles by covalent coupling or in a
non-covalent way [6–9]. Most immobilization strategies require a site-specific
modification of the aptamer; these modifications are commonly introduced during
the aptamer synthesis [10]. Covalent coupling can, e.g., be performed via
carbodiimide coupling chemistry [6]. Non-covalent coupling can be performed by
utilizing affinity ligands (e.g., streptavidin and biotin) [9]; physisorption, e.g.,
between thiol-modified aptamers and gold nanoparticles [7]; or π-stacking between
nucleotide bases of the aptamer and the side walls of single-walled carbon nanotubes
(SWNTs) [8].
To ensure the functionality of nanoparticle-coupled aptamers, some parameters
have to be considered. Aptamers depend on their three-dimensional structure for
target recognition and binding; disrupting the native structure of an aptamer may
lead to a loss of affinity [11]. Therefore the density of immobilized aptamers must be
optimized carefully. Too high densities can result in non-correct folding of aptamers
[12], while too low aptamer density can reduce the binding capacity of the
functionalized nanoparticle. Furthermore the surface charge of the nanoparticle can
affect aptamer folding, e.g., a positive-charged surface can interact electrostatically
with the negative-charged aptamers and lead to aptamer unfolding. In some cases
aptamers that are bound directly to a surface cannot adapt their correct folding
because of their proximity to the surface; in these cases spacers (e.g., poly T spacers)
can be used to increase the distance of the aptamers to the surface and therefore allow
correct folding. The orientation of aptamer immobilization can also affect aptamer
functionality; in this case both 3
0 and 5
0 terminal modifications should be investigated to optimize functionality of the aptamer orientation [13].
If these aspects are taken into account, aptamer-modified nanoparticles can be a
promising tool for medical applications including diagnostics and therapy.
1.2 Aptamer-Modified Nanoparticles and Multivalent
Binding
Nanoparticles hold the potential to carry more than one aptamer, thereby facilitating
multivalent binding with dramatically increased affinity. Here either several copies
Aptamer-Modified Nanoparticles in Medical Applications
163