portions of the aptamer sequence. Here drugs cannot escape the pores until the target
molecule binds to the aptamer resulting in dissociation of the aptamer from the
oligonucleotide (see Fig. 6a). Upon target binding, the aptamer dissociates from the
MSN, and due to the flexibility of the complementary DNAs the MSNs pores are
open and facilitate the release of the drug [103]. Alternatively, pores can be blocked
by aptamer-modified gold nanoparticles (see Fig. 6b). Therefore molecules have to
be coupled to the MSN, to which the used aptamer also binds, but the binding
strength has to be weaker than to the target molecule (e.g., adenosine also binds to
ATP-targeting aptamers, but binding strength of the aptamer is stronger for ATP, so
adenosine is released from the ATP aptamer in the presence of ATP). If there is no
target, the aptamer-modified gold nanoparticles bind to the surface of the MSN and
prevent drug release. In the presence of the target, it will bind to the aptamers,
thereby releasing the aptamer-modified AuNPs from the MSN, the pores aren’t
blocked anymore, and the drug is released [105]. For example, Zhu et al. and He
et al. developed this controlled drug release system using ATP as target molecule to
trigger drug release [103, 105].
The surface of MSN can easily be functionalized with different molecules. If
drugs are bound to MSN by electrostatic interactions with surface molecules, drugs
can be released due to pH shift. For example, Li et al. developed a MSN system with
phosphate-modified inner channels that can bind positively charged doxorubicin via
electrostatic interactions at physiological pH. If the pH decreases, like in tumor
tissue, the charge of the phosphate gets positive, and doxorubicin is released from
the pores. Aptamers were bound to the surface of the MSN for targeted cell binding
and receptor-mediated endocytosis [104]. Figure 6 shows the components of different MSN-based targeted drug delivery systems.
3.1.5 Others
There are some nanomaterials that are less frequently used for drug delivery but also
worth mentioning. These are explained in more detail in the following sections; a
short summary of the systems can be found in Table 4.
Dendrimers
Dendrimers are branched polymers that contain a central inner core. To this core
several repeating groups of the polymer are bound, which themselves can bind
several repeating groups, so they build a branched outer layer [85]. The surface
can be modified with several functional groups, thus providing a wide range of
modifications, e.g., with targeting ligands such as aptamers [106]. Drugs can be
bound inside the dendrimers. Chen et al. developed a sophisticated dendrimer-based
drug delivery system containing three different aptamers for mitochondrial targeting
and to circumvent multidrug resistance (MDR) of tumor cells. The aptamer AS1411
was used for targeting and internalization into nucleolin presenting cells. Furthermore, a cytochrome c targeting aptamer was used for internalization of the
dendrimers into the mitochondria, and an ATP aptamer was used for selective
Aptamer-Modified Nanoparticles in Medical Applications
179
molecule binds to the aptamer resulting in dissociation of the aptamer from the
oligonucleotide (see Fig. 6a). Upon target binding, the aptamer dissociates from the
MSN, and due to the flexibility of the complementary DNAs the MSNs pores are
open and facilitate the release of the drug [103]. Alternatively, pores can be blocked
by aptamer-modified gold nanoparticles (see Fig. 6b). Therefore molecules have to
be coupled to the MSN, to which the used aptamer also binds, but the binding
strength has to be weaker than to the target molecule (e.g., adenosine also binds to
ATP-targeting aptamers, but binding strength of the aptamer is stronger for ATP, so
adenosine is released from the ATP aptamer in the presence of ATP). If there is no
target, the aptamer-modified gold nanoparticles bind to the surface of the MSN and
prevent drug release. In the presence of the target, it will bind to the aptamers,
thereby releasing the aptamer-modified AuNPs from the MSN, the pores aren’t
blocked anymore, and the drug is released [105]. For example, Zhu et al. and He
et al. developed this controlled drug release system using ATP as target molecule to
trigger drug release [103, 105].
The surface of MSN can easily be functionalized with different molecules. If
drugs are bound to MSN by electrostatic interactions with surface molecules, drugs
can be released due to pH shift. For example, Li et al. developed a MSN system with
phosphate-modified inner channels that can bind positively charged doxorubicin via
electrostatic interactions at physiological pH. If the pH decreases, like in tumor
tissue, the charge of the phosphate gets positive, and doxorubicin is released from
the pores. Aptamers were bound to the surface of the MSN for targeted cell binding
and receptor-mediated endocytosis [104]. Figure 6 shows the components of different MSN-based targeted drug delivery systems.
3.1.5 Others
There are some nanomaterials that are less frequently used for drug delivery but also
worth mentioning. These are explained in more detail in the following sections; a
short summary of the systems can be found in Table 4.
Dendrimers
Dendrimers are branched polymers that contain a central inner core. To this core
several repeating groups of the polymer are bound, which themselves can bind
several repeating groups, so they build a branched outer layer [85]. The surface
can be modified with several functional groups, thus providing a wide range of
modifications, e.g., with targeting ligands such as aptamers [106]. Drugs can be
bound inside the dendrimers. Chen et al. developed a sophisticated dendrimer-based
drug delivery system containing three different aptamers for mitochondrial targeting
and to circumvent multidrug resistance (MDR) of tumor cells. The aptamer AS1411
was used for targeting and internalization into nucleolin presenting cells. Furthermore, a cytochrome c targeting aptamer was used for internalization of the
dendrimers into the mitochondria, and an ATP aptamer was used for selective
Aptamer-Modified Nanoparticles in Medical Applications
179