Silica nanogelling of environment-responsive PEGylated polyplexes for enhanced stability and intracellular delivery of siRNA

Noha Gouda, Kanjiro Miyata, R. James Christie, Tomoya Suma, Akihiro Kishimura, Shigeto Fukushima, Takahiro Nomoto, Xueying Liu, Nobuhiro Nishiyama, Kazunori Kataoka

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21 Citations (Scopus)

Abstract

In this study, poly(ethylene glycol) (PEG)-block-polycation/siRNA complexes (PEGylated polyplexes) were wrapped with a hydrated silica, termed "silica nanogelling", in order to enhance their stability and functionality. Silica nanogelling was achieved by polycondensation of soluble silicates onto the surface of PEGylated polyplexes comprising a disulfide cross-linked core. Formation of silica nanogel layer on the PEGylated cross-linked polyplexes was confirmed by particle size increase, surface charge reduction, and elemental analysis of transmission electron micrographs. Silica nanogelling substantially improved polyplex stability against counter polyanion-induced dissociation under non-reductive condition, without compromising the reductive environment-responsive siRNA release triggered by disulfide cleavage. Silica nanogelling significantly enhanced the sequence-specific gene silencing activity of the polyplexes in HeLa cells without associated cytotoxicity, probably due lower endosomal entrapment (or lysosomal degradation) of delivered siRNA. The lower endosomal entrapment of the silica nanogel system could be explained by an accelerated endosomal escape triggered by deprotonated silanol groups in the silica (the proton sponge hypothesis) and/or a modulated intracellular trafficking, possibly via macropinocytosis, as evidenced by the cellular uptake inhibition assay. Henceforth, silica nanogelling of PEGylated siRNA polyplexes is a promising strategy for preparation of stable and functional siRNA delivery vehicles.

Original languageEnglish
Pages (from-to)562-570
Number of pages9
JournalBiomaterials
Volume34
Issue number2
DOIs
Publication statusPublished - Jan 2013

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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    Gouda, N., Miyata, K., Christie, R. J., Suma, T., Kishimura, A., Fukushima, S., Nomoto, T., Liu, X., Nishiyama, N., & Kataoka, K. (2013). Silica nanogelling of environment-responsive PEGylated polyplexes for enhanced stability and intracellular delivery of siRNA. Biomaterials, 34(2), 562-570. https://doi.org/10.1016/j.biomaterials.2012.09.077