Delaminated layered double hydroxide delivers DNA molecules as sandwich nanostructure into cells via a non-endocytic pathway

Ye Li; Wenlong Bao; Hongyang Wu; Junya Wang; Yu Zhang; Yinglang Wan; Dapeng Cao; Dermot O'Hare; Qiang Wang

doi:10.1016/j.scib.2017.04.004

Delaminated layered double hydroxide delivers DNA molecules as sandwich nanostructure into cells via a non-endocytic pathway

Sci Bull (Beijing). 2017 May 30;62(10):686-692. doi: 10.1016/j.scib.2017.04.004. Epub 2017 Apr 13.

Authors

Ye Li¹, Wenlong Bao², Hongyang Wu², Junya Wang³, Yu Zhang⁴, Yinglang Wan², Dapeng Cao⁵, Dermot O'Hare⁶, Qiang Wang⁷

Affiliations

¹ College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, China. Electronic address: liye0223@bjfu.edu.cn.
² College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, China.
³ Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
⁴ College of Environmental Science and Engineering, Beijing Forestry University, Beijing 100083, China.
⁵ State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, China.
⁶ Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.
⁷ College of Environmental Science and Engineering, Beijing Forestry University, Beijing 100083, China. Electronic address: qiangwang@bjfu.edu.cn.

PMID: 36659439
DOI: 10.1016/j.scib.2017.04.004

Abstract

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.

Keywords: DNA; Dissipative particle dynamics simulations; Effective penetration structure; Gene delivery; Layered double hydroxides.