Angew: Nuclease-resistant DNA nanowires modify cell-specific aptamers to achieve selective tumor therapy
DNA nanostructures have shown potential in cancer treatment. However, current clinical practice is hampered by the difficulty in delivering them to cancer cells and the sensitivity to nuclease degradation. To overcome these limitations, this paper reports a DNA nanowire (NW) with high serum stability and active targeting function. The inner core is made of multiple connected DNA double helices, and the outer shell is composed of regularly arranged upright hairpin aptamers. When exposed to the target binding site to allow delivery to the cancer target, all ends of the component are not attacked by nucleases. After 24 hours of incubation in the serum solution, the DNA NW remains intact. Animal imaging and cell apoptosis show that the anti-cancer drugs formulated by NW have long blood circulation time and are highly specific in inducing cancer cell apoptosis. The treatment of tumor-bearing mice validated the therapeutic effect in vivo and proved to be effective for targeted imaging and cancer treatment.
This paper proves that the uniform, biocompatible and orderly arranged core/shell NWs-Aptamer nanocarriers show a significant improvement in nuclease resistance and cell targeting ability. The growth of the linear core can be adjusted by changing the molar ratio of the two modules. The sticky ends of the two modules are suitable for further assembly into a serum-stable outer layer. By surrounding the linear DNA double helix core, a hairpin-like protrusion of the cancer cell protective aptamer is formed. The DNA NWs-Aptamer nanocarrier maintains its structural integrity after 24 hours of incubation in the serum solution, thereby prolonging the blood circulation time.
In addition, DNA carriers have significantly enhanced drug loading capabilities and cancer cell targeting capabilities, including improved binding affinity and specificity, which together contribute to excellent targeted drug delivery. Confocal fluorescence imaging and flow cytometry analysis show that DNA NWs-Aptamer-Dox can specifically induce apoptosis of cancer cells without detecting adverse effects on non-target cells. The anti-tumor efficacy of NWs-Aptamer-Dox in vivo has also been verified. This work shows several advantages, such as high drug loading capacity, long blood circulation time, no modified formulations, ideal binding affinity, high specificity and good biocompatibility. NanoImmuno
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