Tetrahedral framework nucleic acids: Nanokeys unlocking a new era of precision biomedicine

Tetrahedral framework nucleic acids (tFNAs), a crucial component of DNA nanotechnology, have emerged as versatile tools in biomedical research, largely owing to their distinctive structural features and multifaceted capabilities. Recent studies have highlighted the ability of tFNAs to specifically target biological pathways, facilitate cellular uptake, and enhance therapeutic efficacy. tFNAs also show considerable potential in addressing challenges such as drug resistance and poor bioavailability. However, several challenges, including limited in vivo stability, low drug-loading capacity, and potential long-term toxicity, need to be addressed for successful clinical translation. This review comprehensively explores the latest advancements in tFNAs, focusing particularly on their applications and mechanisms in treating a wide array of diseases. From bone diseases to ophthalmic disorders, tFNAs not only promote bone regeneration but also enhance therapeutic efficacy through targeted drug delivery. They also play a role in combating infectious diseases, skin and soft tissue repair, neurological and mental disorders, hepatorenal diseases, and cancer. In addition, tFNAs have demonstrated significant potential in regenerative medicine, immunomodulation, and gene delivery. This work highlights the future potential of DNA nanotechnology in precision medicine, paving the way for next-generation therapeutic strategies.