2 Aptamer-Based Probes for Molecular Imaging
47
As new contrast agent, great efforts are needed to extend the study about aptamers
as imaging molecular probes. To date, most molecular imaging studies regarding the
aptamer focused on the cancer topic. Half of them concentrated on four targets overexpressed in the tumor cell, Nucleolin, Mucin 1, PTK7, and EGFR. It is one reason that
most current aptamers are selected against cancer biomarkers [6]. The other reason
is the SELEX (for systematic evolution of ligands by exponential enrichment), the
most commonly enrichment method of aptamer, is time-consuming and cumbersome
[89, 90]. As the number of aptamers identified each year is increasing, the expansion of its application beyond cancer is possible. For example, some aptamers as
fluorescence imaging probes have been studied in animal models with Alzheimer’s
disease [74, 75]. Then, it is widely known that DNA degrades rapidly in plasma,
whereas a mushrooming number of natural DNA aptamers are applied. Therefore,
the integrity and function of aptamers at several hours after intravenous injection
required evaluation in the study. Next, toxicological studies are needed to confirm
the safety of aptamers in vivo, since aptamers are often considered to be nontoxic and
nonimmunogenic. There are germline-encoded pattern recognition receptors (PRRs)
like Toll-like receptors (TLRs) in the innate immune system to identify and clean
the exogenous DNA. The aptamer might be a potential target to the PRRs, causing
an immune response. In addition, few studies had set up a negative control group in
which aptamer is comprised of a random sequence of the same size and chemistry as
the aptamer in study group. In the situation of lacking control agent modified negative oligonucleotide, it is difficult to distinguish whether the great tumor recognition
effect is due to the interaction between the aptamer with its target or the nonspecific uptake by the target position. Also, for aptamer-based nanoparticles, negatively
charged DNA/RNA aptamer might disrupt substantially and affect the biodistribution
in vivo. Compared to transgenic or in situ transplantable tumor model, most animal
model conducted in studies are nude mice bearing tumor xenografts and these subcutaneous tumors cannot mimic the vascular microenvironment of a tumor. Testing the
biodistribution of the aptamer-based probes in transgenic or in situ transplantable
tumor model would be thus very informative.
Overall, aptamer-based molecular imaging probes or medical imaging agents are
being studied, much attentions have to be paid on clinical transformation research of
every imaging modality, which may accelerate the application process. It is expected
to be a research direction in the future to take advantages of aptamers and construct
multifunctional aptamer-based molecular imaging probes.
Acknowledgments This work was supported by the Major State Basic Research Development Program of China (2017YFA0205201), the National Natural Science Foundation of China
(81422023, 81371596, U1705281, and U1505221), the Fundamental Research Funds for the Central
Universities (20720190088 and 20720200019), and the Program for New Century Excellent Talents
in University, China (NCET-13-0502).
47
As new contrast agent, great efforts are needed to extend the study about aptamers
as imaging molecular probes. To date, most molecular imaging studies regarding the
aptamer focused on the cancer topic. Half of them concentrated on four targets overexpressed in the tumor cell, Nucleolin, Mucin 1, PTK7, and EGFR. It is one reason that
most current aptamers are selected against cancer biomarkers [6]. The other reason
is the SELEX (for systematic evolution of ligands by exponential enrichment), the
most commonly enrichment method of aptamer, is time-consuming and cumbersome
[89, 90]. As the number of aptamers identified each year is increasing, the expansion of its application beyond cancer is possible. For example, some aptamers as
fluorescence imaging probes have been studied in animal models with Alzheimer’s
disease [74, 75]. Then, it is widely known that DNA degrades rapidly in plasma,
whereas a mushrooming number of natural DNA aptamers are applied. Therefore,
the integrity and function of aptamers at several hours after intravenous injection
required evaluation in the study. Next, toxicological studies are needed to confirm
the safety of aptamers in vivo, since aptamers are often considered to be nontoxic and
nonimmunogenic. There are germline-encoded pattern recognition receptors (PRRs)
like Toll-like receptors (TLRs) in the innate immune system to identify and clean
the exogenous DNA. The aptamer might be a potential target to the PRRs, causing
an immune response. In addition, few studies had set up a negative control group in
which aptamer is comprised of a random sequence of the same size and chemistry as
the aptamer in study group. In the situation of lacking control agent modified negative oligonucleotide, it is difficult to distinguish whether the great tumor recognition
effect is due to the interaction between the aptamer with its target or the nonspecific uptake by the target position. Also, for aptamer-based nanoparticles, negatively
charged DNA/RNA aptamer might disrupt substantially and affect the biodistribution
in vivo. Compared to transgenic or in situ transplantable tumor model, most animal
model conducted in studies are nude mice bearing tumor xenografts and these subcutaneous tumors cannot mimic the vascular microenvironment of a tumor. Testing the
biodistribution of the aptamer-based probes in transgenic or in situ transplantable
tumor model would be thus very informative.
Overall, aptamer-based molecular imaging probes or medical imaging agents are
being studied, much attentions have to be paid on clinical transformation research of
every imaging modality, which may accelerate the application process. It is expected
to be a research direction in the future to take advantages of aptamers and construct
multifunctional aptamer-based molecular imaging probes.
Acknowledgments This work was supported by the Major State Basic Research Development Program of China (2017YFA0205201), the National Natural Science Foundation of China
(81422023, 81371596, U1705281, and U1505221), the Fundamental Research Funds for the Central
Universities (20720190088 and 20720200019), and the Program for New Century Excellent Talents
in University, China (NCET-13-0502).