Research advances of tetrahedral framework nucleic acid-based systems in biomedicine

This article reviews the latest research advances of tetrahedral framework nucleic acid (tFNA)-based systems in their fabrication, modification, and the potential applications in biomedicine. TFNA arises from the synthesis of four single-stranded DNA chains. Each chain contains brief sequences that complement those found in the other three, culminating in the creation of a pyramid-shaped nanostructure of approximately 10 nanometers in size. The first generation of tFNA demonstrates inherent compatibility with biological systems and the ability to permeate cell membrane effectively. These attributes translate into remarkable capabilities for regulating various cellular biological processes, fostering tissue regeneration, and modulating immune responses. The subsequent evolution of tFNA introduces enhanced adaptability and a relatively higher degree of biological stability. This advancement encompasses structural modifications, such as the addition of functional domains at the vertices or side arms, integration of low molecular weight pharmaceuticals, and the implementation of diverse strategies aimed at reversing multi-drug resistance in tumor cells or microorganisms. These augmentations empower tFNA-based systems to be utilized in different scenarios, thus broadening their potential applications in various biomedical fields. This article reviews the latest research advances of tetrahedral framework nucleic acid (tFNA)-based systems in their synthesis, modification, biological features, and potential biomedical applications. So far, tFNA-based systems have been proved effective in treating diseases affecting different organs and systems, holding promise as a prospective therapeutic option in the future. [Display omitted]