Zeng Yun, Liu Jiajun, Yang Shuo, Liu Wenyan, Xu Liang, Wang Risheng
Department of Chemistry, Missouri University of Science and Technology, Rolla, MO 65409, USA.
Department of Molecular Biosciences, The University of Kansas, Lawrence, KS 66045, USA.
J Mater Chem B. 2018 Mar 21;6(11):1605-1612. doi: 10.1039/C7TB03223D. Epub 2018 Feb 13.
Self-assembled DNA nanostructures have attracted significant research interest in biomedical applications because of their excellent programmability and biocompatibility. To develop multifunctional drug delivery from DNA nanostructures, considerable key information is still needed for clinical application. Traditional fixed endpoint assays do not reflect the dynamic and heterogeneous responses of cells with regard to drugs, and may lead to the misinterpretation of experimental results. For the first time, an integrated time-lapse live cell imaging system was used to study the cellular internalization and controlled drug release profile of three different shaped DNA origami/doxorubicin (DOX) complexes for three days. Our results demonstrated the dependence of DNA nanostructures on shape for drug delivery efficiency, while the rigid 3D DNA origami triangle frame exhibited enhanced cellular uptake capability, as compared with flexible 2D DNA structures. In addition, the translocation of released DOX into the nucleus was proved by fluorescence microscopy, in which a DOX-loaded 3D DNA triangle frame displayed a stronger accumulation of DOX in nuclei. Moreover, given the facile drug loading and auto fluorescence of the anti-cancer drug, DOX, our results suggest that the DNA nanostructure is a promising candidate, as a label-free nanocarrier, for DOX delivery, with great potential for anticancer therapy as well.
自组装DNA纳米结构因其出色的可编程性和生物相容性，在生物医学应用中引起了广泛的研究兴趣。为了开发基于DNA纳米结构的多功能药物递送系统，临床应用仍需要大量关键信息。传统的固定终点分析方法无法反映细胞对药物的动态和异质性反应，可能导致实验结果的误判。首次使用集成的延时活细胞成像系统，对三种不同形状的DNA折纸/阿霉素（DOX）复合物的细胞内化和控释情况进行了为期三天的研究。我们的结果表明，DNA纳米结构的药物递送效率取决于其形状，与柔性二维DNA结构相比，刚性三维DNA折纸三角形框架具有更强的细胞摄取能力。此外，荧光显微镜证实了释放的DOX易位进入细胞核，其中负载DOX的三维DNA三角形框架在细胞核中显示出更强的DOX积累。此外，鉴于抗癌药物DOX易于负载且具有自发荧光，我们的结果表明，DNA纳米结构作为一种无标记纳米载体，在DOX递送方面很有前景，在抗癌治疗中也具有巨大潜力。
