14 Perspectives of Aptamers for Medical Applications
431
data showed that
18 F labeled HER2 specific aptamer did uptake higher in HER2positive BT474 tumor-bearing mice compared to the that of HER2-negative cell
tumor In PET molecular imaging.
Excellent work from Tan’s group presents the target therapy characteristic of
HER2 aptamer [154]. Authors engineered a HER2 aptamer with ADC trastuzumabDM1 (T-DM1, a newly developed anticancer agent), this complex can efficiently
be internalized into HER2 high expression breasts cancer cells, such as BT474 and
SKBR3, it can also be delivered into the tumor tissue in BT474 xenografted mouse
models to inhibit tumor growth with lower organ toxicity.
Triple-negative breast cancer (TNBC), which accounts for 12–17% of all breast
cancers, lacks expression of the estrogen receptor, progesterone receptor, and HER2,
thus excluding targeted therapy against these proteins [155]. Thus TNBC often leads
to system relapse due to its highly invasive nature and a relatively low response to
therapeutics.
Platelet-derived growth factor receptor β (PDGFRβ) is a transmembrane receptor
tyrosine kinase that contributes to angiogenesis and tumor progression [156, 157],
the expression of PDGFRβ is induced during epithelial-to-mesenchymal transition
(EMT) in breast cancer cells [158]. Still, PDGFRβ also found to be related to stem
traits in mammary epithelial cells [159]. Further evidence showed that PDGFRβ
induces endothelial cell differentiation of mesenchymal TNBC cells and vasculogenic mimicry (VM) [160]. These experimental evidence support targeting this
receptor as therapeutic options.
A research group from Italy generated a nuclease-resistant RNA-PDGFRβaptamer(Gint4.T), this aptamer targets for the extracellular domain of PDGFRβ in
a soluble form (EC-PDGFRβ) with KD of 9.6 nM, they demonstrated that Gint4.T
aptamer could inhibit the PDGFRβ expressed on bone marrow-derived mesenchymal
stem cells (BM-MSCs), in turn block the development of metastasis in TNBC [157].
Treatments with this aptamer block the invasion phenotype of mesenchymal-like
TNBC cells in Matrigel and further confirmed the aptamers ability to suppress the
lung metastasis in a mouse model of TNBC [161].
These excellent works on PDGFRβ-aptamer allow for expansion of this smart
drug to treat the PDGFRβ-positive TNBC in the near future.
Except for PDGFRβ, Mucin 1(MUC1) is another glycoprotein frequently overexpressed in breast cancer which indicates a poor prognosis [162]. Ferreira et al. [163]
identified a 25 merMUC1 DNA aptamer (5TR1), this aptamer can be internalized into
epithelial cancer cells to deliver chemical drugs to the target cell. For example, Luo
et al. [164] constructed a 5TR1 chemically modified Dox drug vector (named 5TR1GC-DOX), the functions of this complex was validated both in vitro and in vivo, the
results show that 5TR1 specifically bind to the malignant breast cancer cell instead
of normal breast cells, targeted drug 5TR1-GC-Dox can also improve the survival
percent of a mouse model of TNBC. This preclinical study provides a possibility to
develop an effective drug to cure TNBC.
CD44 is a transmembrane glycoprotein, it works as a hyaluronic acid receptor
which is present in many types of tumors including breast, prostate, cervical, lung,
ovarian, colorectal, and neuroblastoma [165]. The CD44 receptor [166] has been
431
data showed that
18 F labeled HER2 specific aptamer did uptake higher in HER2positive BT474 tumor-bearing mice compared to the that of HER2-negative cell
tumor In PET molecular imaging.
Excellent work from Tan’s group presents the target therapy characteristic of
HER2 aptamer [154]. Authors engineered a HER2 aptamer with ADC trastuzumabDM1 (T-DM1, a newly developed anticancer agent), this complex can efficiently
be internalized into HER2 high expression breasts cancer cells, such as BT474 and
SKBR3, it can also be delivered into the tumor tissue in BT474 xenografted mouse
models to inhibit tumor growth with lower organ toxicity.
Triple-negative breast cancer (TNBC), which accounts for 12–17% of all breast
cancers, lacks expression of the estrogen receptor, progesterone receptor, and HER2,
thus excluding targeted therapy against these proteins [155]. Thus TNBC often leads
to system relapse due to its highly invasive nature and a relatively low response to
therapeutics.
Platelet-derived growth factor receptor β (PDGFRβ) is a transmembrane receptor
tyrosine kinase that contributes to angiogenesis and tumor progression [156, 157],
the expression of PDGFRβ is induced during epithelial-to-mesenchymal transition
(EMT) in breast cancer cells [158]. Still, PDGFRβ also found to be related to stem
traits in mammary epithelial cells [159]. Further evidence showed that PDGFRβ
induces endothelial cell differentiation of mesenchymal TNBC cells and vasculogenic mimicry (VM) [160]. These experimental evidence support targeting this
receptor as therapeutic options.
A research group from Italy generated a nuclease-resistant RNA-PDGFRβaptamer(Gint4.T), this aptamer targets for the extracellular domain of PDGFRβ in
a soluble form (EC-PDGFRβ) with KD of 9.6 nM, they demonstrated that Gint4.T
aptamer could inhibit the PDGFRβ expressed on bone marrow-derived mesenchymal
stem cells (BM-MSCs), in turn block the development of metastasis in TNBC [157].
Treatments with this aptamer block the invasion phenotype of mesenchymal-like
TNBC cells in Matrigel and further confirmed the aptamers ability to suppress the
lung metastasis in a mouse model of TNBC [161].
These excellent works on PDGFRβ-aptamer allow for expansion of this smart
drug to treat the PDGFRβ-positive TNBC in the near future.
Except for PDGFRβ, Mucin 1(MUC1) is another glycoprotein frequently overexpressed in breast cancer which indicates a poor prognosis [162]. Ferreira et al. [163]
identified a 25 merMUC1 DNA aptamer (5TR1), this aptamer can be internalized into
epithelial cancer cells to deliver chemical drugs to the target cell. For example, Luo
et al. [164] constructed a 5TR1 chemically modified Dox drug vector (named 5TR1GC-DOX), the functions of this complex was validated both in vitro and in vivo, the
results show that 5TR1 specifically bind to the malignant breast cancer cell instead
of normal breast cells, targeted drug 5TR1-GC-Dox can also improve the survival
percent of a mouse model of TNBC. This preclinical study provides a possibility to
develop an effective drug to cure TNBC.
CD44 is a transmembrane glycoprotein, it works as a hyaluronic acid receptor
which is present in many types of tumors including breast, prostate, cervical, lung,
ovarian, colorectal, and neuroblastoma [165]. The CD44 receptor [166] has been