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.

Nanomaterials as Theranostic Agents for Cancer Therapy

“…DNA nanostructures have demonstrated promises in cancer therapy, but their clinical application is hindered by challenges related to effective delivery into cancer cells and vulnerability to nuclease degradation. To address the limitations, Xue et al 57 present a novel approach�a periodically ordered nick-hidden DNA nanowire (NW) with remarkable serum stability and active targeting capabilities. This innovative structure consists of a central core composed of interlinked DNA double helices and an outer shell made up of regularly positioned, upright hairpin aptamers.…”

Aptamer-engineered (nano)materials for theranostic applications

“…Aptamer-DOX DNA NWs can enter the blood circulation through endocytosis of cells in blood and are able to accumulate in target tissues. The aptamer can bind to the membrane protein tyrosine kinase-7 (PTK7) overexpressed by cells and it can fold into a hairpin structure [85]. Another group of researchers, led by Ouyang, developed a DNA nanoscale precision-guided missile (D-PGM) for the targeted delivery of therapeutic agents to target cells, to improve the effectiveness of treatment.…”

Harnessing Nucleic Acids Nanotechnology for Bone/Cartilage Regeneration

“…Reproduced with permission. [42] Copyright 2020, Wiley-VCH. The typical examples of nucleic acids nanotechnology.…”