Li Ye, Bao Wenlong, Wu Hongyang, Wang Junya, Zhang Yu, Wan Yinglang, Cao Dapeng, O'Hare Dermot, Wang Qiang
College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, China.
College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, China.
Sci Bull (Beijing). 2017 May 30;62(10):686-692. doi: 10.1016/j.scib.2017.04.004. Epub 2017 Apr 13.
Layered double hydroxides (LDHs) are effective molecular carriers in cytological research, gene therapy, and transgenic applications. Herein, we investigated the internalization behavior of the LDH-DNA bioconjugates via a microscopic approach and analyzed the internalization pathway by dissipative particle dynamics (DPD) simulations. We experimentally found that LDH can efficiently carry DNA into the nucleus of cell in BY-2 suspension cells. Furthermore, atomic force microscopy and X-ray diffraction analysis demonstrated that the LDH-DNA bioconjugates mainly exist as a DNA-LDH-DNA sandwich complex, while the LDH-DNA-LDH sandwich complex and DNA-LDH complex cannot be excluded. The DPD simulations further indicated that only the DNA-LDH-DNA sandwich structure could penetrate the plasma membrane (PM), while PM is impermeable to the LDH-DNA-LDH sandwich complex and the DNA-LDH complex. This work provides novel perspective for understanding the membrane penetration mechanism of LDH nano-sheets and new insights into the design of novel molecular delivery systems.
层状双氢氧化物（LDHs）在细胞学研究、基因治疗和转基因应用中是有效的分子载体。在此，我们通过显微镜方法研究了LDH-DNA生物共轭物的内化行为，并通过耗散粒子动力学（DPD）模拟分析了内化途径。我们通过实验发现，LDH能够有效地将DNA携带到BY-2悬浮细胞的细胞核中。此外，原子力显微镜和X射线衍射分析表明，LDH-DNA生物共轭物主要以DNA-LDH-DNA夹心复合物的形式存在，而LDH-DNA-LDH夹心复合物和DNA-LDH复合物也不能排除。DPD模拟进一步表明，只有DNA-LDH-DNA夹心结构能够穿透质膜（PM），而PM对LDH-DNA-LDH夹心复合物和DNA-LDH复合物是不可渗透的。这项工作为理解LDH纳米片的膜穿透机制提供了新的视角，并为新型分子递送系统的设计提供了新的见解。
