2′-Fluoroarabinonucleic Acid Nanostructures as Stable Carriers for Cellular Delivery in the Strongly Acidic Environment

DNA nanotechnology is powerful in constructing programmable nanostructures with distinct dimensions, sizes, and shapes. However, natural DNA molecules are prone to nuclease degradation, thus limiting the in vivo applications of such DNA nanostructures. 2'-Fluoroarabinonucleic acid (FANA) is a chemically modified oligonucleotide with similar base pairing properties to DNA and exhibits superior physical and chemical stabilities. In this work, FANA molecules were used to construct double crossover nanostructures, and it was demonstrated that incorporation of FANA conferred nucleic acid nanostructures with increased thermal stability and stronger nuclease resistance. More importantly, FANA nanostructures were able to maintain the structural integrity in the strongly acidic environment (pH 1.2). Last, such FANA nanostructures functioned well in acting as stable carriers of small-molecule cargoes for cellular delivery in simulated gastric fluid, while the DNA counterparts were mostly degraded. Collectively, these results demonstrated that FANA self-assembly was not only a substantial complement to the structural DNA nanotechnology but also an appealing molecular tool for in vivo biomedical applications.