Jump to main content
Jump to site search

Issue 42, 2016
Previous Article Next Article

Precise redox-sensitive cleavage sites for improved bioactivity of siRNA lipopolyplexes

Author affiliations

Abstract

Lipo-oligomers have been proven as potent siRNA carriers based on stable electrostatic and hydrophobic complex formation and endosomal membrane destabilization. Although high stability of siRNA polyplexes is desirable in the extracellular space and cellular uptake, intracellular disassembly is important for the cytosolic release of siRNA and RNA-induced silencing complex formation. To improve the release, bioreducible sequence-defined lipo-oligomers were synthesized by solid-phase assisted synthesis using the disulfide building block Fmoc-succinoyl-cystamine for precise positioning of a disulfide unit between a lipophilic diacyl (bis-myristyl, bis-stearyl or bis-cholestanyl) domain and an ionizable oligocationic siRNA binding unit. Reducible siRNA polyplexes show higher gene silencing efficacy and lower cytotoxicity than their stable analogs, consistent with glutathione-triggered siRNA release and reduced lytic activity.

Graphical abstract: Precise redox-sensitive cleavage sites for improved bioactivity of siRNA lipopolyplexes

Back to tab navigation

Supplementary files

Publication details

The article was received on 21 Jul 2016, accepted on 06 Oct 2016 and first published on 07 Oct 2016


Article type: Paper
DOI: 10.1039/C6NR05767E
Citation: Nanoscale, 2016,8, 18098-18104
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    Precise redox-sensitive cleavage sites for improved bioactivity of siRNA lipopolyplexes

    P. M. Klein, S. Reinhard, D. Lee, K. Müller, D. Ponader, L. Hartmann and E. Wagner, Nanoscale, 2016, 8, 18098
    DOI: 10.1039/C6NR05767E

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements