Advancements in Engineering Tetrahedral Framework Nucleic Acids for Biomedical Innovations

Tetrahedral framework nucleic acids (tFNAs) are renowned for their controllable self-assembly, exceptional programmability, and excellent biocompatibility, which have led to their widespread application in the biomedical field. Beyond these features, tFNAs demonstrate unique chemical and biological properties including high cellular uptake efficiency, structural bio-stability, and tissue permeability, which are derived from their distinctive 3D structure. To date, an extensive range of tFNA-based nanostructures are intelligently designed and developed for various biomedical applications such as drug delivery, gene therapy, biosensing, and tissue engineering, among other emerging fields. In addition to their role in drug delivery systems, tFNAs also possess intrinsic properties that render them highly effective as therapeutic agents in the treatment of complex diseases, including arthritis, neurodegenerative disorders, and cardiovascular diseases. This dual functionality significantly enhances the utility of tFNAs in biomedical research, presenting valuable opportunities for the development of next-generation medical technologies across diverse therapeutic and diagnostic platforms. Consequently, this review comprehensively introduces the latest advancements of tFNAs in the biomedical field, with a focus on their benefits and applications as drug delivery nanoplatforms, and their inherent capabilities as therapeutic agents. Furthermore, the current limitations, challenges, and future perspectives of tFNAs are explored.