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

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. A periodically ordered nick‐hidden DNA nanowire composed of six distinct oligonucleotide components was developed as a powerful drug‐delivery vehicle for the accurate diagnosis and targeted therapy of cancers (see picture). Owing to the high serum stability and active targeting functionality of the construct, NWs loaded with doxorubicin exhibited a long blood‐circulation time and high specificity in inducing cancer‐cell apoptosis.