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

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 biocon- jugates 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 anal- ysis 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 simu- lations 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.

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.ó 2017 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.