DNA tetrahedral nanostructures for the biomedical application and spatial orientation of biomolecules

DNA not only plays a vital role in nature as fundamental hereditary material for storing genetic material, but also serves as well-defined functional material, for example, building blocks for the assembly of nanoscale bioarchitectures by Watson-Crick base-pairing interaction. With the development of molecular biology, biotechnology and nanoscience, structural DNA nanotechnology has achieved numerous advances, contributing to the construction of various DNA nanostructures ranging from discrete objects to one dimensional (1D), two dimensional (2D), and three dimensional (3D) architectures. Among them, DNA tetrahedral nanoarchitecture is intensively studied because of simple 3D structure, easy design and unique properties, such as high rigidity, desirable biostability and efficient cellular uptake without auxiliary species. This review summarizes the research progress in the assembly of DNA tetrahedral objects and outlines the applications in biosensing, drug delivery and targeted therapy. Moreover, the dependence of biological activity of biomolecules on DNA tetrahedronmediated spatially-controlled arrangement and great potential applications are discussed. In addition, the challenges in the design and clinic applications of DNA tetrahedron-based platforms are described, the perspectives towards biomedical applications are foreseen, and our understandings on further studies of DNA tetrahedron are provided, aiming to motivate the development of DNA nanotechnology and interdisciplinary research.