accumulate in tissue with leaky vasculature such as inflamed tissue or tumors
[79]. This effect, called enhanced permeability and retention effect (EPR effect),
alters the biodistribution and pharmacokinetics of a drug, so it can reduce the
systemic side effects of nanoparticle-bound drugs and increase drug concentrations
in target tissues [5, 79].
The addition of a targeting ligand such as an aptamer further increases the
specificity of the system and can promote target binding and cellular uptake of
nanoparticles (e.g., via receptor-mediated endocytosis) [5, 79]. This results in higher
cytotoxicity of aptamer-modified nanoparticle systems and therefore can reduce the
amount of the drug that is needed for therapy [81, 82].
There are several possibilities to use aptamer-modified nanoparticles for therapeutic applications. A frequently used approach is the use of nanoparticles for drug
delivery (see Sect. 3.1). Another therapeutic application using aptamer-modified
nanoparticles is the photothermal and photodynamic therapy, which uses the characteristics of the nanoparticle material to create damaging effects to cells upon
irradiation with certain wavelengths (see Sect. 3.2). In Sect. 3.3 some less frequently
used applications of aptamer-modified nanoparticles for therapeutic applications are
shown.
3.1 Drug Delivery with Aptamer-Modified Nanoparticles
The most common approach of using aptamer-modified nanoparticles for therapeutic
applications is the delivery of drugs to the target tissue with nanoparticles as carrier
materials. By the modification with aptamers, these drug-nanoparticle conjugates
obtain their specificity for the target cells. Several different materials can be used as
carrier materials. Their specific advantages and disadvantages will be discussed
below. In Table 4 a summary of different aptamer-based targeted drug delivery
systems (TDDS) is shown.
3.1.1 Gold Nanoparticles
Gold nanoparticles (AuNPs) can be produced with different methods; commonly
citrate-based methods resulting in citrate-functionalized AuNPs or the BrustSchiffrin method resulting in alkanethiolate-modified AuNPs are used. Preparation
methods usually offer high yields and result in nanoparticles with characteristic sizes
and shapes (e.g., spherical or nonspherical). The sizes of AuNPs can be between a
few nanometer and over 200 nm. The cytotoxicity of AuNPs is dependent on their
size and surface modification and has to be investigated for each system individually.
The surface area to volume ratio of AuNPs is usually high, and the surface can be
modified in many different ways (e.g., with thiols or amines) [83]. Targeting ligands
can easily be added to AuNPs, e.g., by physisorption of thiol-modified aptamers or
by coupling to functional groups on the nanoparticle surface [7, 83]. For targeted
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[79]. This effect, called enhanced permeability and retention effect (EPR effect),
alters the biodistribution and pharmacokinetics of a drug, so it can reduce the
systemic side effects of nanoparticle-bound drugs and increase drug concentrations
in target tissues [5, 79].
The addition of a targeting ligand such as an aptamer further increases the
specificity of the system and can promote target binding and cellular uptake of
nanoparticles (e.g., via receptor-mediated endocytosis) [5, 79]. This results in higher
cytotoxicity of aptamer-modified nanoparticle systems and therefore can reduce the
amount of the drug that is needed for therapy [81, 82].
There are several possibilities to use aptamer-modified nanoparticles for therapeutic applications. A frequently used approach is the use of nanoparticles for drug
delivery (see Sect. 3.1). Another therapeutic application using aptamer-modified
nanoparticles is the photothermal and photodynamic therapy, which uses the characteristics of the nanoparticle material to create damaging effects to cells upon
irradiation with certain wavelengths (see Sect. 3.2). In Sect. 3.3 some less frequently
used applications of aptamer-modified nanoparticles for therapeutic applications are
shown.
3.1 Drug Delivery with Aptamer-Modified Nanoparticles
The most common approach of using aptamer-modified nanoparticles for therapeutic
applications is the delivery of drugs to the target tissue with nanoparticles as carrier
materials. By the modification with aptamers, these drug-nanoparticle conjugates
obtain their specificity for the target cells. Several different materials can be used as
carrier materials. Their specific advantages and disadvantages will be discussed
below. In Table 4 a summary of different aptamer-based targeted drug delivery
systems (TDDS) is shown.
3.1.1 Gold Nanoparticles
Gold nanoparticles (AuNPs) can be produced with different methods; commonly
citrate-based methods resulting in citrate-functionalized AuNPs or the BrustSchiffrin method resulting in alkanethiolate-modified AuNPs are used. Preparation
methods usually offer high yields and result in nanoparticles with characteristic sizes
and shapes (e.g., spherical or nonspherical). The sizes of AuNPs can be between a
few nanometer and over 200 nm. The cytotoxicity of AuNPs is dependent on their
size and surface modification and has to be investigated for each system individually.
The surface area to volume ratio of AuNPs is usually high, and the surface can be
modified in many different ways (e.g., with thiols or amines) [83]. Targeting ligands
can easily be added to AuNPs, e.g., by physisorption of thiol-modified aptamers or
by coupling to functional groups on the nanoparticle surface [7, 83]. For targeted
172
A. Eilers et al.