7 Aptamers for Personalized Therapeutics
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gold nanosphere (HAuNS) and doxorubicin. This synthesized conjugate could selectively kill tumor cells [120]. For nuclear uptake of anticancerous drugs, aptamernanoparticle conjugates have also been used. A fascinating dual-aptamer conjugate was orchestrated which could target both PSMA-negative as well as PSMApositive prostate cancer cells. DUP-1 peptide aptamer (targeting PSMA-negative
cells) and A10 RNA aptamer (targeting PSMA-positive cells) have been conjugated
with streptavidin to constitute dual aptamer for targeted drug delivery [121].
Anti-EpCAM aptamer conjugated with polymerosomes containing Dox loaded
PEG-PLGA has been effectively used against adenocarcinoma cell lines. Similar
promising results were reported by in vivo study in mice model where Epirubicin is loaded to aptamer-functionalized super-paramagnetic iron oxide nanoparticles (SPION). This conjugate effectively reduced the growth of tumor [122].
Doxorubicin-conjugated PSMA aptamer-functionalized super-paramagnetic iron
oxide nanoparticles (TCL-SPIONs) were used in LNCaP xenograft mouse model
which demonstrated selective and targeted drug delivery [123]. A number of studies
published in peer-reviewed journals have confirmed the effective therapeutic applications of conjugates of NP-Apt effectively. Similarly for tumor-specific drug delivery
and monitoring the therapeutic response, dual-aptamer conjugates have been used
for multiple targets [109, 124].
7.3.5 Antidote Aptamer for Controlled Therapy
In the current era the main goal of cancer therapeutics is the eradication of malignant
cells. Therapeutic drug efficacy in target cells and toxicity due to chemical drugs are
two sides of the same coin and the successful therapies demand balance between
them. In different diseases especially cancers, the circulation half-lives ranging up to
several weeks has been demonstrated by humanized monoclonal antibodies, enabling
less frequent drug administration. In the context of long exposure, such patientfriendly treatments can improve quality of life on one end and also enhance the
antitumor efficacy. However, unexpected toxicity from drugs with prolonged halflives can pose severe side effects and may possibly extend toxic effects unless the
circulating drug is inactivated.
The same theme applies to aptamers in terms of aptamer-based therapeutics. To
control the action time of therapeutic aptamers, antidote aptamers are used. These
antidote aptamers are in fact the corresponding complementary sequence of the target
aptamers just like sense and antisense strands of mRNA. Complementarity-based
hybridization of the aptamer and antidote leads to changes, especially conformational
and structural, resulting in the loss of target binding ability of the aptamer [125, 126].
This strategy has been successfully applied to control drug action time in in vivo
studies. It was showed that antidote oligonucleotide 5-2 which is complementary to
aptamer Peg-9.3t blocked the anticoagulant activity of Peg-9.3t aptamer in merely
197
gold nanosphere (HAuNS) and doxorubicin. This synthesized conjugate could selectively kill tumor cells [120]. For nuclear uptake of anticancerous drugs, aptamernanoparticle conjugates have also been used. A fascinating dual-aptamer conjugate was orchestrated which could target both PSMA-negative as well as PSMApositive prostate cancer cells. DUP-1 peptide aptamer (targeting PSMA-negative
cells) and A10 RNA aptamer (targeting PSMA-positive cells) have been conjugated
with streptavidin to constitute dual aptamer for targeted drug delivery [121].
Anti-EpCAM aptamer conjugated with polymerosomes containing Dox loaded
PEG-PLGA has been effectively used against adenocarcinoma cell lines. Similar
promising results were reported by in vivo study in mice model where Epirubicin is loaded to aptamer-functionalized super-paramagnetic iron oxide nanoparticles (SPION). This conjugate effectively reduced the growth of tumor [122].
Doxorubicin-conjugated PSMA aptamer-functionalized super-paramagnetic iron
oxide nanoparticles (TCL-SPIONs) were used in LNCaP xenograft mouse model
which demonstrated selective and targeted drug delivery [123]. A number of studies
published in peer-reviewed journals have confirmed the effective therapeutic applications of conjugates of NP-Apt effectively. Similarly for tumor-specific drug delivery
and monitoring the therapeutic response, dual-aptamer conjugates have been used
for multiple targets [109, 124].
7.3.5 Antidote Aptamer for Controlled Therapy
In the current era the main goal of cancer therapeutics is the eradication of malignant
cells. Therapeutic drug efficacy in target cells and toxicity due to chemical drugs are
two sides of the same coin and the successful therapies demand balance between
them. In different diseases especially cancers, the circulation half-lives ranging up to
several weeks has been demonstrated by humanized monoclonal antibodies, enabling
less frequent drug administration. In the context of long exposure, such patientfriendly treatments can improve quality of life on one end and also enhance the
antitumor efficacy. However, unexpected toxicity from drugs with prolonged halflives can pose severe side effects and may possibly extend toxic effects unless the
circulating drug is inactivated.
The same theme applies to aptamers in terms of aptamer-based therapeutics. To
control the action time of therapeutic aptamers, antidote aptamers are used. These
antidote aptamers are in fact the corresponding complementary sequence of the target
aptamers just like sense and antisense strands of mRNA. Complementarity-based
hybridization of the aptamer and antidote leads to changes, especially conformational
and structural, resulting in the loss of target binding ability of the aptamer [125, 126].
This strategy has been successfully applied to control drug action time in in vivo
studies. It was showed that antidote oligonucleotide 5-2 which is complementary to
aptamer Peg-9.3t blocked the anticoagulant activity of Peg-9.3t aptamer in merely