Advances in biological applications of self-assembled DNA tetrahedral nanostructures

In recent years, there has been a rapid progress in the development of DNA nanomaterials for biological applications. Owing to their unsurpassed editability, various DNA nanomaterials with well-documented biocompatibility and relative stability have been developed. Among these tetrahedral DNA nanostructures (TDNs), as typical multi-arm DNA tiles for 3D polyhedral, is a major research focus owing to their structural and biological features. TDNs have yielded satisfactory results as biological regulators, biosensors, and targeted delivery vehicles. Extensive studies on TDNs have revealed that TDNs alone could regulate several cellular processes, such as migration, proliferation, differentiation, and autophagy. Further, their editability enables control of the spatial distribution of biosensors, thereby promoting accuracy and efficiency. Finally, various modification procedures allow attachment of nucleic acids, aptamers, peptides, antibodies, and various low-molecular-weight drugs to the TDNs, thereby yielding a novel targeted delivery system. This review summarizes recent research progress on TDNs in these aforementioned major areas. These discoveries might be of great therapeutic value in regenerative medicine, gene delivery, targeted chemotherapy, and other related fields. We also illustrate the emerging challenges in the clinical application of TDNs, as well as future development opportunities.