Functional DNA nanostructures for theranostic applications

There has been tremendous interest in constructing nanostructures by exploiting the unparalleled ability of DNA molecules in self-assembly. We have seen the appearance of many fantastic, "art-like" DNA nanostructures in one, two, or three dimensions during the last two decades. More recently, much attention has been directed to the use of these elegant nanoobjects for applications in a wide range of areas. Among them, diagnosis and therapy (i.e., theranostics) are of particular interest given the biological nature of DNA.One of the major barricades for the biosensor design lies in the restricted target accessibility at the solid-water interface. DNA nanotechnology provides a convenient approach to well control the biomolecule-confined surface to increase the ability of molecular recognition at the biosensing interface. For example, tetrahedral DNA nanostructures with thiol modifications can be self-assembled at the gold surface with high reproducibility. Since DNA tetrahedra are highly rigid and well-defined structures with atomic precision and versatile functionality, they provide scaffolds for anchoring of a variety of biomolecular probes (DNA, aptamers, peptides, and proteins) for biosensing. Significantly, this DNA nanostructure-based biosensing platform greatly increases target accessibility and improves the sensitivity for various types of molecular targets (DNA, RNA, proteins, and small molecules) by several orders of magnitude.In an alternative approach, DNA nanostructures provide a framework for the development of dynamic nanosensors that can function inside the cell. DNA tetrahedra are found to be facilely cell permeable and can sense and image specific molecules in cells. More importantly, these DNA nanostructures can be efficient drug delivery nanocarriers. Since they are DNA molecules by themselves, they have shown excellent cellular biocompatibility with minimal cytotoxicity. As an example, DNA tetrahedra tailored with CpG oligonucleotide drugs have shown greatly improved immunostimulatory effects that makes them a highly promising nanomedicine. By taking them together, we believe these functionalized DNA nanostructures can be a type of intelligent theranostic nanodevice for simultaneous sensing, diagnosis, and therapy inside the cell.