Aptamer Generated by Cell-SELEX for Specific Targeting of Human Glioma Cells

Abstract

The most prevalent primary brain tumors are gliomas, which start in the glial cells. Although there have been significant technological advances in surgery and radio-chemotherapy, the prognosis and survival of patients with malignant gliomas remain poor. For routine diagnosis of glioma, computed tomography and magnetic resonance imaging primarily depend on anatomical changes and fail to detect the cellular changes that occur early in the development of malignant gliomas. Therefore, it is urgent to find effective molecular diagnostic tools to detect early stages of malignant gliomas. Currently, cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) technology is one effective tool to obtain DNA or RNA aptamers capable of differentiating the molecular signatures among different types of cell lines. Using cell-SELEX, we generated and characterized an aptamer, termed S6-1b, that can distinguish the molecular differences between glioma cell line SHG44 and human astrocytes. Under the conditions of 4 and 37 °C, respectively, the dissociation constants of aptamer−cell interaction were both measured in the low nanomolar range. The aptamer S6-1b also exhibited excellent selectivity, making it suitable for use in a complex biological environment. Furthermore, the aptamer can effectively target glioma cells for in vivo fluorescence imaging of tumors. The target type of aptamer S6-1b was identified as a cell membrane protein. Our work indicates that aptamer S6-1b has diagnostic and therapeutic potential to specifically deliver imaging or therapeutic agents to malignant gliomas.

Applications of Aptamer-Bound Nanomaterials in Cancer Therapy

“… ( A ) Basic principle of the cell-SELEX method and applications for ( B ) cell imaging and ( C ) in vivo imaging. Reprinted with permission from [ 29 ]. Copyright © 2020 American Chemical Society.…”

“…It is well known that aptamers have a highly selective recognition ability that helps them recognize targets [ 26 , 27 , 28 ]. Aptamers are single-stranded DNAs or RNAs evolved through systematic evolution of ligands by exponential enrichment (SELEX) technology [ 29 , 30 ] and they are widely employed, as shown in Figure 1 . Aptamers can fold into various secondary structures, further forming three-dimensional structures, which contribute to the interaction between aptamers and their targets through various forces, such as hydrophobic interaction and electrostatic attraction [ 31 , 32 ].…”

“…In principle, an aptamer sequence can be deleted, added, or united flexibly to endow aptamers with tunable recognition ability to better identify targets. Stimulus–response strategies including light, pH, ligand binding, and other cues which have been developed into the design of aptamer-based nanomaterials [ 27 , 28 , 29 ]. In short, these merits make aptamers ideal candidates for disease diagnosis and therapeutics owing to their ability to deliver therapeutic cargoes into cancer cells, diseased tissue, and organs.…”

“…Finally, we discuss perspectives on challenges and future applications of aptamer-bound nanomaterials in cancer therapy. [29]. Copyright © 2020 American Chemical Society.…”

Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX

“…SELEX relies on repeating positive and negative selection processes that eliminate weakly binding and non- binding sequences. Targets can be small molecules, proteins, or even whole cells 21 , 22 . Aptamers have quickly emerged as a novel and powerful class of ligands with excellent potential for diagnostic and therapeutic applications, particularly in cancer-based applications 23 , 24 .…”