9 Aptamers for the Diagnosis of Malign Tumors
259
organelles and membrane proteins comparing to antibodies [120]. Using the approach
of SPECT/CT imaging, researchers compared the performances of
111 Indium (In)labeled aptamers and
111 In-antibodies. The results proved that
111 In-labeled aptamers
can be better uptaken by tumor tissues due to their smaller size [121]. These studies
verified that the aptamers offer better performance over antibodies for application in
molecular imaging of subcellular and in vivo.
Tissue imaging based on aptamers has great potential, getting the benefit of the
continuously discovered cancer-specific aptamers with high target specificity [122].
To date, several studies investigated aptamers-based cancer characterizations through
immunohistochemical (IHC) staining, mass spectrometry (MS), or other approaches.
Immunohistochemical (IHC) staining is a classic approach for the identification
of tumor-associated biomarkers in formalin-fixed or frozen tissue sections in clinical
histopathological diagnosis [123]. In this approach, the cancer protein biomarkerstargeting antibody labeled with a reporter group (as enzymes, fluorophores, et al.) is
utilized for the identification of the cancer cells in the tissue section. Benefit from
several advantages over antibodies, the aptamers have been considered as an alternative to antibodies in the IHC staining for disease information visualization [124]. The
pancreatic-cancer-specific RNA aptamers were labeled by Cy3 fluorophore for the
identification of cancer patient specimens from normal tissues. This probe showed
a strong fluorescent signal within cancer tissue associated with the low survival rate
of patients [125]. In another study, the fluorescent prostate cancer-targeting probe
was established with Cy5-labeled DNA aptamer DML-7. The probe showed much
stronger fluorescence intensity on metastatic cancer tissue specimens than those on
the normal or non-metastatic tissues [126]. An aptamer-based immunofluorescence
technique was developed for frozen tissue section staining of colorectal cancer (CRC)
patients. The Cy3 fluorophore-labeled anti-EpCAM DNA aptamer (SYL3C-Cy3)
was established as an effective probe for identification of EpCAM-positive CRC
cells within tissue samples [127] (Fig. 9.8a). In another study, seven aptamers were
identified through the Cell-SELEX approach for specifically targeting metastatic
CRC LoVo cells. Then, one of these aptamers (namely aptamer W3) was conjugated
to quantum dots through biotin-streptavidin linkage. This QD-aptamer molecular
probe can stain the cancer tissue specimens and quantify the fluorescence signal
through microscopy [128].
Mass spectrometry tissue imaging (MSI) owns a substantial impact in cancer diagnosis and research, through imaging the biomolecules changes relative to the disease
progression, metastasis, and prognosis [129]. The laser desorption/ionization MS
(LDI-MS) methods have been developed for analyzing the distribution of nanomaterials within the tissue specimen [130]. For example, a cancer diagnosis platform
was established with functional nanoparticles, including nucleolin-binding aptamer
(AS1411) modified gold nanoparticles (Apt-AuNPs) and poly(catechin) cappedAuNPs (Au@PC NPs). The gold cluster ions were exfoliated from Apt-AuNPs and
performed as signal amplifiers for nucleolin-positive tissue section imaging. This
aptamer-based tissue MSI was then tested on human breast tumor tissue compared
to the normal ones. It was found that the tumor tissue samples other than the normal
ones could be labeled with the Apt-AuNPs, and LDI-MS imaging was acquired
259
organelles and membrane proteins comparing to antibodies [120]. Using the approach
of SPECT/CT imaging, researchers compared the performances of
111 Indium (In)labeled aptamers and
111 In-antibodies. The results proved that
111 In-labeled aptamers
can be better uptaken by tumor tissues due to their smaller size [121]. These studies
verified that the aptamers offer better performance over antibodies for application in
molecular imaging of subcellular and in vivo.
Tissue imaging based on aptamers has great potential, getting the benefit of the
continuously discovered cancer-specific aptamers with high target specificity [122].
To date, several studies investigated aptamers-based cancer characterizations through
immunohistochemical (IHC) staining, mass spectrometry (MS), or other approaches.
Immunohistochemical (IHC) staining is a classic approach for the identification
of tumor-associated biomarkers in formalin-fixed or frozen tissue sections in clinical
histopathological diagnosis [123]. In this approach, the cancer protein biomarkerstargeting antibody labeled with a reporter group (as enzymes, fluorophores, et al.) is
utilized for the identification of the cancer cells in the tissue section. Benefit from
several advantages over antibodies, the aptamers have been considered as an alternative to antibodies in the IHC staining for disease information visualization [124]. The
pancreatic-cancer-specific RNA aptamers were labeled by Cy3 fluorophore for the
identification of cancer patient specimens from normal tissues. This probe showed
a strong fluorescent signal within cancer tissue associated with the low survival rate
of patients [125]. In another study, the fluorescent prostate cancer-targeting probe
was established with Cy5-labeled DNA aptamer DML-7. The probe showed much
stronger fluorescence intensity on metastatic cancer tissue specimens than those on
the normal or non-metastatic tissues [126]. An aptamer-based immunofluorescence
technique was developed for frozen tissue section staining of colorectal cancer (CRC)
patients. The Cy3 fluorophore-labeled anti-EpCAM DNA aptamer (SYL3C-Cy3)
was established as an effective probe for identification of EpCAM-positive CRC
cells within tissue samples [127] (Fig. 9.8a). In another study, seven aptamers were
identified through the Cell-SELEX approach for specifically targeting metastatic
CRC LoVo cells. Then, one of these aptamers (namely aptamer W3) was conjugated
to quantum dots through biotin-streptavidin linkage. This QD-aptamer molecular
probe can stain the cancer tissue specimens and quantify the fluorescence signal
through microscopy [128].
Mass spectrometry tissue imaging (MSI) owns a substantial impact in cancer diagnosis and research, through imaging the biomolecules changes relative to the disease
progression, metastasis, and prognosis [129]. The laser desorption/ionization MS
(LDI-MS) methods have been developed for analyzing the distribution of nanomaterials within the tissue specimen [130]. For example, a cancer diagnosis platform
was established with functional nanoparticles, including nucleolin-binding aptamer
(AS1411) modified gold nanoparticles (Apt-AuNPs) and poly(catechin) cappedAuNPs (Au@PC NPs). The gold cluster ions were exfoliated from Apt-AuNPs and
performed as signal amplifiers for nucleolin-positive tissue section imaging. This
aptamer-based tissue MSI was then tested on human breast tumor tissue compared
to the normal ones. It was found that the tumor tissue samples other than the normal
ones could be labeled with the Apt-AuNPs, and LDI-MS imaging was acquired