Nuclease-resistant signaling nanostructures made entirely of DNA oligonucleotides

Nucleic acid probes have the advantages of excellent biocompatibility, biodegradability, low toxicity and remarkable programmability. However, the low biostability of nucleic acid probes under complex physiological conditions limits the in vivo application. Despite impressive progresses in the development of inorganic material-mediated biostable nucleic acid nanostructures in the biomedical field, uncertain cytotoxicity of composite nanocarriers have hindered their application in living systems. In the field of biomedicine, as a promising alternative capable of avoiding potential cytotoxicity, the biologically stable nanostructures composed entirely of DNA oligonucleotides have been rapidly developed in recent years, offering an exciting in vivo tool for cancer diagnosis and clinical treatment. In this review, we summarize the recent advances in the studies of nuclease-resistant DNA nanostructures with different geometrical shapes, such as tetrahedron, octahedron, DNA triangular prism (DTP), DNA nanotubes and DNA origami, introduce innovative assembly strategies, and discuss unique structural advantages and especially biological applications in cellular imaging and targeted drug delivery in an organism. Finally, we conclude with challenges and an outlook of the future development in this rapidly expanding field.