Technical and Macromolecular Chemistry, Paderborn University, Warburger Strasse 100, 33098, Paderborn, Germany.
Present address: Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702-1201, USA.
Chembiochem. 2019 Nov 18;20(22):2818-2823. doi: 10.1002/cbic.201900369. Epub 2019 Oct 11.
DNA nanostructures have emerged as intriguing tools for numerous biomedical applications. However, in many of those applications and most notably in drug delivery, their stability and function may be compromised by the biological media. A particularly important issue for medical applications is their interaction with proteins such as endonucleases, which may degrade the well-defined nanoscale shapes. Herein, fundamental insights into this interaction are provided by monitoring DNase I digestion of four structurally distinct DNA origami nanostructures (DONs) in real time and at a single-structure level by using high-speed atomic force microscopy. The effect of the solid-liquid interface on DON digestion is also assessed by comparison with experiments in bulk solution. It is shown that DON digestion is strongly dependent on its superstructure and flexibility and on the local topology of the individual structure.
DNA 纳米结构已成为众多生物医学应用中引人入胜的工具。然而，在许多此类应用中，尤其是在药物输送方面，其稳定性和功能可能会受到生物介质的影响。对于医疗应用而言，一个特别重要的问题是它们与内切酶等蛋白质的相互作用，这些蛋白质可能会破坏其明确的纳米级形状。通过使用高速原子力显微镜实时且在单结构水平上监测四种结构截然不同的 DNA 折纸纳米结构（DONs）的 DNA 酶 I 消化，为这种相互作用提供了基本的见解。通过与在体相溶液中的实验进行比较，评估了固液界面对 DON 消化的影响。结果表明，DON 的消化强烈依赖于其超结构和灵活性以及单个结构的局部拓扑结构。
