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Q. Lv et al.
and circulating tumor cells participate in the cancer progression, and provide the
possibility to detect cancer in the early stage. The cancer-specific markers are potential targets for cancer detection and personal medicine [3]. Antibodies with high
affinity have become a powerful tool for cancer diagnosis and therapy, and pave the
way to reveal the pathogenesis. However, confined to differences between batches,
cross-reactivity, immunogenicity, high costs, and difficulty of chemical modification,
antibodies still face limitations to provide effective tumor diagnosis [4, 5].
Nucleic acid aptamers are derived from the Systematic Evolution of Ligands
by Exponential enrichment (SELEX) process. They have emerged as alternative
biorecognition elements due to their unique characteristics [6, 7]. Aptamers are
normally highly structured, single-stranded oligonucleotides as RNA or ssDNA
ranging about 15–100 nt, recognizing the specific target molecules as unique tertiary
structures [8]. Aptamers are called “chemical antibodies” that interact with high
affinity and selectivity to their targets. However, compared with antibodies, aptamers
exhibit excellent chemical stability over a wide range of pH, temperature, and
ionic strength [9]. They can be denatured reversibly with molecular activity [10].
Also, aptamers can penetrate deep tissues with little immunogenicity due to their
smaller size. They are readily synthesized and easily modified with high reproducibility [11]. For example, aptamers can conjugate several functional moieties at
any desired position through the facile solid-state phosphoramidite processes. As
natural nucleic acids, aptamers have the intrinsic features to hybridize with complementary strands [12]. Based on these advantages, aptamers can be exploited to
produce versatile molecular probes, sensors, drug carriers, and other platforms. Since
the first discovery in 1990, aptamers have attracted much attention in academic and
commercial industries.
Aptamers exhibit great potential in clinical diagnosis such as in biosensors for
detecting cancer biomarkers, circulating tumor cells and cancer-associated exosome
sensing, in vivo solid tumor tissue and molecular imaging, as well as in immune
histochemistry. In this chapter, we present a summary of the recent process of
aptamer application in the diagnosis of malign tumors, including cancer biomarkers
discovery and detection, circulating tumor cells sensing, tissue section and molecular
imaging, and also, exosomes sensing. Finally, we discuss the challenges and future
perspectives, and possible solutions for aptamer in diagnosis, especially in the new
aptamers’ discovery, deficiencies of aptasensors, and their potential application in
cancer clinical research in the future.
9.2 Aptamers in Cancer Biomarkers Discovery
Cancer biomarkers include cancer-associated genes, proteins, exosomes, and cells
[13]. The discovery of cancer biomarkers can facilitate early diagnosis of cancer,
thus providing interventions to prevent and manage the disease progression and prognosis. Specific proteins and their expression variations are generally accepted and
established as cancer biomarkers due to their dynamic reflection of physiology [14].
Q. Lv et al.
and circulating tumor cells participate in the cancer progression, and provide the
possibility to detect cancer in the early stage. The cancer-specific markers are potential targets for cancer detection and personal medicine [3]. Antibodies with high
affinity have become a powerful tool for cancer diagnosis and therapy, and pave the
way to reveal the pathogenesis. However, confined to differences between batches,
cross-reactivity, immunogenicity, high costs, and difficulty of chemical modification,
antibodies still face limitations to provide effective tumor diagnosis [4, 5].
Nucleic acid aptamers are derived from the Systematic Evolution of Ligands
by Exponential enrichment (SELEX) process. They have emerged as alternative
biorecognition elements due to their unique characteristics [6, 7]. Aptamers are
normally highly structured, single-stranded oligonucleotides as RNA or ssDNA
ranging about 15–100 nt, recognizing the specific target molecules as unique tertiary
structures [8]. Aptamers are called “chemical antibodies” that interact with high
affinity and selectivity to their targets. However, compared with antibodies, aptamers
exhibit excellent chemical stability over a wide range of pH, temperature, and
ionic strength [9]. They can be denatured reversibly with molecular activity [10].
Also, aptamers can penetrate deep tissues with little immunogenicity due to their
smaller size. They are readily synthesized and easily modified with high reproducibility [11]. For example, aptamers can conjugate several functional moieties at
any desired position through the facile solid-state phosphoramidite processes. As
natural nucleic acids, aptamers have the intrinsic features to hybridize with complementary strands [12]. Based on these advantages, aptamers can be exploited to
produce versatile molecular probes, sensors, drug carriers, and other platforms. Since
the first discovery in 1990, aptamers have attracted much attention in academic and
commercial industries.
Aptamers exhibit great potential in clinical diagnosis such as in biosensors for
detecting cancer biomarkers, circulating tumor cells and cancer-associated exosome
sensing, in vivo solid tumor tissue and molecular imaging, as well as in immune
histochemistry. In this chapter, we present a summary of the recent process of
aptamer application in the diagnosis of malign tumors, including cancer biomarkers
discovery and detection, circulating tumor cells sensing, tissue section and molecular
imaging, and also, exosomes sensing. Finally, we discuss the challenges and future
perspectives, and possible solutions for aptamer in diagnosis, especially in the new
aptamers’ discovery, deficiencies of aptasensors, and their potential application in
cancer clinical research in the future.
9.2 Aptamers in Cancer Biomarkers Discovery
Cancer biomarkers include cancer-associated genes, proteins, exosomes, and cells
[13]. The discovery of cancer biomarkers can facilitate early diagnosis of cancer,
thus providing interventions to prevent and manage the disease progression and prognosis. Specific proteins and their expression variations are generally accepted and
established as cancer biomarkers due to their dynamic reflection of physiology [14].