drug delivery based on AuNPs, drugs can be integrated into the system by three
commonly used ways that are described below (see Fig. 3).
The first way is the intercalation of drugs into hairpin regions of DNA (see
Fig. 3a). For example, the drug doxorubicin is able to intercalate into DNA hairpins.
As specificity-mediating ligands, aptamers can be bound to the surface in addition to
the hairpin DNA [7].
The second way is the direct intercalation of drugs into aptamers (see Fig. 3b). For
example, the aptamer A10 has a GC-rich stem region, where the drug doxorubicin
can intercalate [84]. This intercalation often takes place at GC-rich parts of oligonucleotides, e.g., in G-quadruplex structures [85].
Thirdly the drug can be loaded to the surface of AuNPs (see Fig. 3c). For
example, Taghdisi et al. loaded gold nanoparticles with the drug daunorubicin
[86]. Figure 3 shows the components of different AuNP-based targeted drug delivery
systems.
Additionally AuNPs offer the opportunity of photodynamic therapy which is
discussed in Sect. 3.2.1. One disadvantage of AuNPs in drug delivery is that only the
surface of the AuNPs or the surface-bound ligands can be used as a drug carrier.
Some other nanoparticle types do also allow the utilization of the nanoparticle
volume to enhance loading capacity, as discussed in the next paragraphs.
3.1.2 Liposomes and Micelles
Liposomes usually consist of a bilayer of natural or synthetic phospholipids (e.g.,
phosphatidylcholine or phosphatidylethanolamine (see Fig. 4) [85, 87]. The bilayer
structure enables encapsulation of hydrophilic drugs inside of the core and hydrophobic drugs inside of the lipid bilayer [85]. At body temperature the bilayers are in a
fluid state, making them leaky for encapsulated drugs. If cholesterol is added, the
structure of the liposomes gets more stable, and unintended drug release can be
prevented [87]. Liposomes can be prepared in different ways; the first described
method was the rehydration of a thin film of lipids with aqueous solvents, which was
generated by organic solvent evaporation in a round bottom flask. The size can
further be reduced by sonication or extrusions through a polycarbonate membrane.
One limitation of this method is the rather low encapsulation efficiency
[87, 88]. Another method is the addition of lipids dissolved in an organic solvent
into an aqueous drug solution (solvent injection technique) and subsequent removal
of the organic solvent [87, 89]. However, removal of the organic solvent can be
difficult. By using microfluidics, liposomes with a defined size can be produced
continuously, thereby offering the opportunity for an industrial preparation method
in a large scale [87, 90]. One drawback of liposomes is their short half-life in vivo.
However, this can be improved by surface modification with polyethylene glycol
(PEG). PEG can prevent plasma protein binding and therefore increase the half-life
of liposomes (“stealth liposome”) [87].
Targeting ligands like aptamers can be attached, e.g., via coupling to maleimide
or N-hydroxysuccinimide-activated PEG-modified phospholipids [91, 92]. A
Aptamer-Modified Nanoparticles in Medical Applications
175
commonly used ways that are described below (see Fig. 3).
The first way is the intercalation of drugs into hairpin regions of DNA (see
Fig. 3a). For example, the drug doxorubicin is able to intercalate into DNA hairpins.
As specificity-mediating ligands, aptamers can be bound to the surface in addition to
the hairpin DNA [7].
The second way is the direct intercalation of drugs into aptamers (see Fig. 3b). For
example, the aptamer A10 has a GC-rich stem region, where the drug doxorubicin
can intercalate [84]. This intercalation often takes place at GC-rich parts of oligonucleotides, e.g., in G-quadruplex structures [85].
Thirdly the drug can be loaded to the surface of AuNPs (see Fig. 3c). For
example, Taghdisi et al. loaded gold nanoparticles with the drug daunorubicin
[86]. Figure 3 shows the components of different AuNP-based targeted drug delivery
systems.
Additionally AuNPs offer the opportunity of photodynamic therapy which is
discussed in Sect. 3.2.1. One disadvantage of AuNPs in drug delivery is that only the
surface of the AuNPs or the surface-bound ligands can be used as a drug carrier.
Some other nanoparticle types do also allow the utilization of the nanoparticle
volume to enhance loading capacity, as discussed in the next paragraphs.
3.1.2 Liposomes and Micelles
Liposomes usually consist of a bilayer of natural or synthetic phospholipids (e.g.,
phosphatidylcholine or phosphatidylethanolamine (see Fig. 4) [85, 87]. The bilayer
structure enables encapsulation of hydrophilic drugs inside of the core and hydrophobic drugs inside of the lipid bilayer [85]. At body temperature the bilayers are in a
fluid state, making them leaky for encapsulated drugs. If cholesterol is added, the
structure of the liposomes gets more stable, and unintended drug release can be
prevented [87]. Liposomes can be prepared in different ways; the first described
method was the rehydration of a thin film of lipids with aqueous solvents, which was
generated by organic solvent evaporation in a round bottom flask. The size can
further be reduced by sonication or extrusions through a polycarbonate membrane.
One limitation of this method is the rather low encapsulation efficiency
[87, 88]. Another method is the addition of lipids dissolved in an organic solvent
into an aqueous drug solution (solvent injection technique) and subsequent removal
of the organic solvent [87, 89]. However, removal of the organic solvent can be
difficult. By using microfluidics, liposomes with a defined size can be produced
continuously, thereby offering the opportunity for an industrial preparation method
in a large scale [87, 90]. One drawback of liposomes is their short half-life in vivo.
However, this can be improved by surface modification with polyethylene glycol
(PEG). PEG can prevent plasma protein binding and therefore increase the half-life
of liposomes (“stealth liposome”) [87].
Targeting ligands like aptamers can be attached, e.g., via coupling to maleimide
or N-hydroxysuccinimide-activated PEG-modified phospholipids [91, 92]. A
Aptamer-Modified Nanoparticles in Medical Applications
175