Abstract
Aptamer binding has been used effectively for diagnostics, in-vivo targeting of therapeutics, and the construction and control of nanomachines. Nanostructures that respond to pH by releasing or changing affinity to a target have also been used for in vivo delivery, and in the construction of sensors and re-usable nanomachines. There are many applications that use aptamers together with pH-responsive materials, notably the targeted delivery of chemotherapeutics. However, the number of reported applications that directly use pH to control aptamer binding is small. In this review, we first discuss the use of aptamers with pH-responsive nanostructures for chemotherapeutic and other applications. We then discuss applications that use pH to denature or otherwise disrupt the binding of aptamers. Finally, we discuss motifs using non-canonical nucleic acid base pairing that can shift conformation in response to pH, followed by an overview of engineered pH-controlled aptamers designed using those motifs.
Highlights
In recent years, aptamers have become a useful molecular recognition tool, with applications ranging from biosensors, to affinity purification, to integration in nanoscale machinery [1,2,3]
In 2015, Zhang et al designed artificial micelles composed of two polymers: one pH-responsive, and one decorated with aptamers targeting nucleolin, a membrane protein overexpressed on cancer cells that allows internalization when bound by an aptamer [10]
It was noted that the metal-organic framework (MOF) could be used repeatedly, indicating that the immobilization of the aptamer was not disrupted by the low pH and the aptamers were able to refold and regain binding capacity when reintroduced into a neutral solution [27]
Summary
Aptamers have become a useful molecular recognition tool, with applications ranging from biosensors, to affinity purification, to integration in nanoscale machinery [1,2,3]. Aptamers can act as recognition elements, filling many of the same roles as antibodies; aptamers have several advantages over antibodies that make them attractive for therapeutic and biotechnological applications [4] These include ease of chemical modification, improved stability over time and at variable pH or temperature, reversible conformation change in response to stimulus, and quick and reliable synthesis in vitro [5,6]. One advantage of using pH as a control element is that altering the pH of a solution produces only salts as waste, while other control elements may leave waste compounds that can interfere with later steps or potential re-usability of the system [8,11] Combinations of these two elements have potential applications in the construction of nanomachines, targeting and delivery of in vivo nanostructures and therapeutics, and control of ligand binding in larger structures such as sensors, diagnostics, and purification columns [8,12]. “passive” systems are those whereby the natural pH responsive properties of the nucleic acid sequence were discovered and utilized, while “engineered” systems include those where known pH responsive motifs have been deliberately or rationally included into a sequence
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