Tetrahedral DNA frameworks for biosensing and imaging analysis in living cells

DNA is the primary genetic material that is highly compatible with biological system, and its intrinsic property of complementary base pairing can be programmed for analysis. However, single-stranded DNA probes present challenges as they are difficult to internalize into cells and can easily decompose in the cell microenvironment. In recent years, the development of framework nucleic acids (FNAs) has enabled DNA nanostructures to emerge as promising materials for bioimaging, drug delivery, and biosensor design. These probes offer several advantages, including high biological stability, efficient cell internalization, low dynamic limitations, and diverse signal output. Therefore, it is important to review and summarize the critical role of framework design in DNA-based biosensor construction for the advancement of DNA nanotechnology and its application in bioanalysis. This article provides an overview of the development and limitations of DNA nanostructures in different dimensions and highlights the endocytosis of tetrahedral DNA frameworks (TDF) and their applications in biosensing and imaging. Finally, existing signal output modes are introduced to provide a comprehensive understanding of the potential applications of TDF.