Periodically Ordered, Nuclease‐Resistant DNA Nanowires Decorated with Cell‐Specific Aptamers as Selective Theranostic Agents

Abstract

DNA nanostructures have shown potential in cancer therapy. However, their clinical application is hampered by the difficulty to deliver them into cancer cells and susceptibility to nuclease degradation. To overcome these limitations, we report herein a periodically ordered nick‐hidden DNA nanowire (NW) with high serum stability and active targeting functionality. The inner core is made of multiple connected DNA double helices, and the outer shell is composed of regularly arranged standing‐up hairpin aptamers. All termini of the components are hidden from nuclease attack, whereas the target‐binding sites are exposed to allow delivery to the cancer target. The DNA NW remained intact during incubation for 24 h in serum solution. Animal imaging and cell apoptosis showed that NWs loaded with an anticancer drug displayed long blood‐circulation time and high specificity in inducing cancer‐cell apoptosis, thus validating this approach for the targeted imaging and therapy of cancers.

Biosensors Based on Bivalent and Multivalent Recognition by Nucleic Acid Scaffolds

“…In addition to these examples, the nucleic acid elongation concept has been used for other designs. For example, CEM cells have been recognized and visualized using DNA nanowires [106], and nanocentipedes have been constructed using the HCR for the imaging of specific cells (SMMC-7721 cells) [107].…”

DNA nanostructure-based nucleic acid probes: construction and biological applications

“…In recent years, Lu et al used this kind of nanowire as a targeted therapeutic agent. 22 It demonstrates an ideal therapeutic vehicle for tumor-targeted imaging and inducing tumor cell apoptosis.…”

Multivalent self-assembled nano string lights for tumor-targeted delivery and accelerated biomarker imaging in living cells and in vivo

“…In the past decades, DNA-based nanoprobes have attracted great interest from researchers for sensing biomarkers in living cells, because they have easy programmability and high intracellular delivery efficiency. 1–3 For instance, upconversion nanoparticles (UCNPs), 4–6 graphene oxide (GO), 7–9 MnO 2 nanosheets, 10–12 metal–organic frameworks, 13–15 AuNPs, 16–18 and DNA nanostructures 19–21 have been reported as nanocarriers to construct DNA-based nanoprobes to realize sensitive biomarker detection. However, inorganic nanocarrier-based nanoprobes suffer from non-negligible cytotoxicity or the problems of nonspecific release and environmental susceptibility.…”