State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering , Hunan University , Changsha , Hunan 410082 , China.
Anal Chem. 2019 Feb 19;91(4):2610-2614. doi: 10.1021/acs.analchem.8b05706. Epub 2019 Feb 4.
DNA hydrogels are biocompatible and are suitable for many biomedical applications. However, to be useful imaging probes or drug carriers, the ordinary bulk size of DNA hydrogels must be overcome. Here we put forward a new strategy for fabricating a novel and simple protein-scaffolded DNA nanohydrogel, constructed through a direct DNA self-assembly using three types of streptavidin (SA)-based DNA tetrad for the activation of imaging and targeting therapy of cancer cells. The DNA nanohydrogels are easily prepared, and we show that by varying the initial concentration of DNA tetrad, it is possible to finely control their size within nanoscale range, which are favorable as carriers for intracellular imaging and transport. By further incorporating therapeutic agents and tumor-targeting MUC1 aptamer, these multifunctionalized SA-scaffolded DNA nanohydrogels (SDH) can specifically target cancer cells and selectively release the preloaded therapeutic agents via a structure switching when in an ATP-rich intracellular environment, leading to the activation of the fluorescence and efficient treatment of cancer cells. With the advantages of facile modular design and assembly, effective cellular uptake, and excellent biocompatibility, the method reported here has the potential for the development of new tunable DNA nanohydrogels with multiple synergistic functionalities for biological and biomedical applications.
DNA 水凝胶具有生物相容性，适用于许多生物医学应用。然而，为了成为有用的成像探针或药物载体，必须克服普通块状 DNA 水凝胶的尺寸问题。在这里，我们提出了一种新的策略来构建一种新型简单的基于蛋白质支架的 DNA 纳米水凝胶，该水凝胶通过使用三种基于链霉亲和素（SA）的 DNA 四联体进行直接 DNA 自组装来构建，用于激活癌细胞的成像和靶向治疗。DNA 纳米水凝胶易于制备，我们表明通过改变 DNA 四联体的初始浓度，可以在纳米范围内精细控制其尺寸，这有利于作为细胞内成像和运输的载体。通过进一步掺入治疗剂和肿瘤靶向 MUC1 适体，这些多功能化的 SA 支架 DNA 纳米水凝胶（SDH）可以特异性地靶向癌细胞，并在富含 ATP 的细胞内环境中通过结构切换选择性释放预装载的治疗剂，从而激活荧光并有效治疗癌细胞。由于具有易于模块化设计和组装、有效的细胞摄取和优异的生物相容性等优点，这里报道的方法有可能开发具有多种协同功能的新型可调谐 DNA 纳米水凝胶，用于生物和生物医学应用。
