Advancing Aptamers as Molecular Probes for Cancer Theranostic Applications—The Role of Molecular Dynamics Simulation

Abstract

Theranostics cover emerging technologies for cell biomarking for disease diagnosis and targeted introduction of drug ingredients to specific malignant sites. Theranostics development has become a significant biomedical research endeavor for effective diagnosis and treatment of diseases, especially cancer. An efficient biomarking and targeted delivery strategy for theranostic applications requires effective molecular coupling of binding ligands with high affinities to specific receptors on the cancer cell surface. Bioaffinity offers a unique mechanism to bind specific target and receptor molecules from a range of non‐targets. The binding efficacy depends on the specificity of the affinity ligand toward the target molecule even at low concentrations. Aptamers are fragments of genetic materials, peptides, or oligonucleotides which possess enhanced specificity in targeting desired cell surface receptor molecules. Aptamer–target binding results from several inter‐molecular interactions including hydrogen bond formation, aromatic stacking of flat moieties, hydrophobic interaction, electrostatic, and van der Waals interactions. Advancements in Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assay has created the opportunity to artificially generate aptamers that specifically bind to desired cancer and tumor surface receptors with high affinities. This article discusses the potential application of molecular dynamics (MD) simulation to advance aptamer‐mediated receptor targeting in targeted cancer therapy. MD simulation offers real‐time analysis of the molecular drivers of the aptamer‐receptor binding and generate optimal receptor binding conditions for theranostic applications. The article also provides an overview of different cancer types with focus on receptor biomarking and targeted treatment approaches, conventional molecular probes, and aptamers that have been explored for cancer cells targeting.

Neuroblastoma GD2 Expression and Computational Analysis of Aptamer-Based Bioaffinity Targeting

“…This method combines the principles of cytology with the specificity of immunological reactions to perform localization and/or quantification of cells with antigens of interest. In other words, the method thrives on the presence and development of antibodies or other high-affinity agents such as aptamers [51,52]. Although aptamers promise to overcome some of the limitations associated (in terms of selection difficulties, selectivity problems, preparation difficulties, high costs of production, stability, and cross-reactivity issues), there is little to no research reports on their application for GD2 characterization.…”

“…Its application in the detection and treatment of several types of malignancy has been studied extensively with impressive results in binding specificities to various types of small molecules including antigens and toxins [61][62][63][64]. Beneficial properties of aptamers include their ability to be conjugated with other molecules to improve their stability and attach fluorescence molecule for imaging, to name a few [51,60,65,66]. In conjunction with flow cytometry, aptamers have been used to diagnose a myriad of tumors and other diseases targeting different cell surface antigens.…”

An aptamer highly specific to cellulose enables the analysis of the association of cellulose with matrix cell wall polymers in vitro and in muro

“…These are short fragments of single‐stranded nucleic acid (RNA or DNA), often called “chemical antibodies,” as they selectively and strongly bind to other molecules. This association is governed by the same diversity of intramolecular bonds known from immunoglobulin paratope–epitope interactions (Jeevanandam et al., 2020). However, unlike mAbs, they are developed through an in vitro process (Systematic evolution of ligands by exponential enrichment (SELEX); Ali et al., 2019), thus eliminating the need for animal hosts or immune response, and consequently enabling the development of aptamers for virtually any target (Stoltenburg et al., 2007), even complex molecular structures connected by non‐covalent bonds.…”

The role of SAXS and molecular simulations in 3D structure elucidation of a DNA aptamer against lung cancer

“…Obtaining the structure is challenging; [16][17][18][19][20] however, atomistic computer simulations, such as molecular dynamics (MD), can generate plausible molecular models that represent multiple minima that a molecule can adopt in solution. [21][22][23] Ranking these structures, that is, predicting which of them are more probable, is a very difficult computational task because of the tiny energy differences between these isomers, which necessitates the use of expensive computational methods for a reliable ranking. Some methods are available for modeling oligonucleotides.…”