Non-thiolated spherical nucleic acids for biosensors and assembly of nanomaterials

Abstract

Spherical nucleic acids (SNAs) refer to a nanoparticle core decorated with a high density of single-stranded DNA or RNA. SNAs have garnered significant attention for their unique physicochemical properties and advantages in biomedical, nanotechnology and biosensing applications. The preparation of traditional SNAs typically relies on the strong bonding between thiolated DNA and gold nanoparticles (AuNPs) to ensure a high-density and stable DNA attachment. Interestingly, non-thiolated DNA also strongly interacts with gold surfaces through the coordination of its nucleobases, enabling the preparation of cost-effective non-thiolated SNAs. In this review, we introduce the adsorption properties of DNA on AuNPs, followed by a review of the current methods for the synthesis of non-thiolated SNAs and a discussion of their stability based on existing data. The reviewed methods include salt-aging, low-pH, freezing, microwaving, and thermal drying. Most methods rely on a poly-adenine block to anchor onto the surface of AuNPs. Furthermore, two types of non-thiolated SNA products are discussed, which are characterized by their DNA density as a function of the length of the poly-adenine block. Finally, we briefly outline the current applications of SNAs, including biosensing and DNA-directed assembly, and discuss potential future developments.