Time-lapse live cell imaging to monitor doxorubicin release from DNA origami nanostructures.
Time-lapse live cell imaging to monitor doxorubicin release from DNA origami nanostructures.
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DOI：
10.1039/c7tb03223d
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发表时间：
2018-03-21
期刊：
影响因子：
--
通讯作者：
Wang R
中科院分区：
文献类型：
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作者：
Zeng Y;Liu J;Yang S;Liu W;Xu L;Wang R
自组装DNA纳米结构具有良好的可编程性和生物相容性，在生物医学领域的应用引起了人们极大的研究兴趣。为了开发基于DNA纳米结构的多功能药物载体，临床应用还需要大量的关键信息。传统的固定终点分析方法不能反映细胞对药物的动态和异质性反应，可能会导致对实验结果的误解。首次使用集成的延时活细胞成像系统研究了三种不同形状的DNA折纸/阿霉素(DOX)复合体的细胞内化和控释特性。我们的结果表明，DNA纳米结构依赖于形状对药物传递效率的依赖，而刚性3D DNA折纸三角形框架与柔性2D DNA结构相比显示出更强的细胞摄取能力。此外，荧光显微镜证实了释放的DOX向细胞核内的移位，其中负载DOX的3D DNA三角形框架显示DOX在细胞核中有较强的积聚。此外，考虑到抗癌药物DOX的简单载药和自发荧光，我们的结果表明，DNA纳米结构作为一种无标记的纳米载体，是一种很有前途的候选药物，在抗癌治疗方面也具有巨大的潜力。DNA折纸纳米结构具有良好的可编程性和生物相容性，是一种很有前途的药物载体。
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. DNA origami nanostructures can serve as a promising carrier for drug delivery due to the outstanding programmability and biocompatibility.