7 Aptamers for Personalized Therapeutics
195
the specificity and selectivity of small molecules with predetermined cytotoxicity
must be considered during drug-designing procedures for complex diseases, and
it can be accomplished via optimization of medicinal chemistry or pharmaceutical
formulation procedures [106]. In contrast, drug-ligand conjugates could fulfill the
goal of targeted therapy. In this kind of drug-ligand conjugates, the ligands recognize
disease-implicated receptors specifically and release conjugated drugs to the target
site. Functional linkers are used for linking drugs with ligands. In fact, ligands do not
have direct therapeutic effects, however, they ensure stability of conjugates and also
allow conditional drug release in diseased cells. Among varying ligands for targeted
drug delivery, monoclonal antibodies are reputable contenders for specific target
recognition and biological regulation, thus providing an emerging and innovative
class of disease treatment agents.
Alternatively, aptamers being nucleotides in contrast to antibodies are of great
interest for designing aptamer-drug conjugates (ApDCs) for targeted therapies [107].
ApDC soften consists of a guidance (aptamer) and a warhead (drug) when noncovalently connected, which serve as a simple but effective approach for disease
treatment in modern era. Aptamer when used for targeted drug delivery, the therapeutic cargo needs to be covalently linked to aptamers via additional linkers. Zhu et al.
synthesized adducts of anthracyclines with synthetic DNA including aptamers. The
conjugation was mediated using formaldehyde [108]. Doxorubicin was conjugated
using a hydrazone linker with DNA aptamer sgc8, which selectively targets protein
tyrosine kinase 7 (PTK7) [109]. Alongside aptamer-drug conjugates, aptamers also
permit targeted delivery of a variety of molecules, like nanoparticles, toxins, photosensitizers to targeted cells and other drug-containing carriers through the conjugation process, by applying prodrug strategies. For instance, an aptamer-tethered long
linear dsDNA structure, named a ‘DNA nanotrain’ (aptNTr), has been established to
transport anticancer drugs and bioimaging agents to targeted cancer cells. Here the
double-stranded DNA serves as a carrier loaded with high density of doxorubicin.
In vivo studies of the above-mentioned model in xenograft tumor model exhibited
enhanced antitumor efficacy and reduced side effects of drugs delivered by aptNTrs.
Similarly, in another study, poly-aptamer-drug approach was applied. This multivalent system was constructed by rolling circle amplification by means of a leukemia
cell-binding aptamer and doxorubicin-loaded DNA strands. On account of aptamer
multivalency, targeting and cellular uptake of the drug were enhanced as compared
to the monovalent counterpart [110].
7.3.3 Aptamer Liposome Conjugates
Liposomes were extensively used as drug-delivery vehicles because of low toxicity and the significant stability of drugs by encapsulation. Apta-mosomes were
synthesized by functionalization of Dox-encapsulated liposomes with aptamers.
These apta-mosomes provided a superior choice to the intercalation of Dox into
the PMSA RNA aptamer by conferring specificity and greater Dox delivery toward
195
the specificity and selectivity of small molecules with predetermined cytotoxicity
must be considered during drug-designing procedures for complex diseases, and
it can be accomplished via optimization of medicinal chemistry or pharmaceutical
formulation procedures [106]. In contrast, drug-ligand conjugates could fulfill the
goal of targeted therapy. In this kind of drug-ligand conjugates, the ligands recognize
disease-implicated receptors specifically and release conjugated drugs to the target
site. Functional linkers are used for linking drugs with ligands. In fact, ligands do not
have direct therapeutic effects, however, they ensure stability of conjugates and also
allow conditional drug release in diseased cells. Among varying ligands for targeted
drug delivery, monoclonal antibodies are reputable contenders for specific target
recognition and biological regulation, thus providing an emerging and innovative
class of disease treatment agents.
Alternatively, aptamers being nucleotides in contrast to antibodies are of great
interest for designing aptamer-drug conjugates (ApDCs) for targeted therapies [107].
ApDC soften consists of a guidance (aptamer) and a warhead (drug) when noncovalently connected, which serve as a simple but effective approach for disease
treatment in modern era. Aptamer when used for targeted drug delivery, the therapeutic cargo needs to be covalently linked to aptamers via additional linkers. Zhu et al.
synthesized adducts of anthracyclines with synthetic DNA including aptamers. The
conjugation was mediated using formaldehyde [108]. Doxorubicin was conjugated
using a hydrazone linker with DNA aptamer sgc8, which selectively targets protein
tyrosine kinase 7 (PTK7) [109]. Alongside aptamer-drug conjugates, aptamers also
permit targeted delivery of a variety of molecules, like nanoparticles, toxins, photosensitizers to targeted cells and other drug-containing carriers through the conjugation process, by applying prodrug strategies. For instance, an aptamer-tethered long
linear dsDNA structure, named a ‘DNA nanotrain’ (aptNTr), has been established to
transport anticancer drugs and bioimaging agents to targeted cancer cells. Here the
double-stranded DNA serves as a carrier loaded with high density of doxorubicin.
In vivo studies of the above-mentioned model in xenograft tumor model exhibited
enhanced antitumor efficacy and reduced side effects of drugs delivered by aptNTrs.
Similarly, in another study, poly-aptamer-drug approach was applied. This multivalent system was constructed by rolling circle amplification by means of a leukemia
cell-binding aptamer and doxorubicin-loaded DNA strands. On account of aptamer
multivalency, targeting and cellular uptake of the drug were enhanced as compared
to the monovalent counterpart [110].
7.3.3 Aptamer Liposome Conjugates
Liposomes were extensively used as drug-delivery vehicles because of low toxicity and the significant stability of drugs by encapsulation. Apta-mosomes were
synthesized by functionalization of Dox-encapsulated liposomes with aptamers.
These apta-mosomes provided a superior choice to the intercalation of Dox into
the PMSA RNA aptamer by conferring specificity and greater Dox delivery toward