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Inorganic nanoparticle mediated delivery of siRNA

Wednesday (08.05.2019)
15:50 - 16:10
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RNA interference (RNAi) is a post-transcriptional gene regulatory mechanism, in which small interfering RNA (siRNA) initiates the cleavage of target mRNA strands. Since its discovery, RNAi has emerged as promising technology for influencing gene expressions. Nevertheless, the delivery of siRNAs into a cell is still challenging due to poor intracellular uptake, limited chemical stability of siRNAs molecules and cell toxicity of current transfection agents.[1,2,3]

Our approach is to use nanoporous silica nanopartilces (NPSNPs) as delivery platform for siRNAs. In the past decade, NPSNPs have emerged as promising basis for designing tailored delivery systems for biomolecules such as small molecule drugs, proteins or nucleic acids. Among other positive features these materials exhibit high surface areas, high permanent porosities and reactive silanol groups at the surface, which can easily be modified. Moreover, NPSNPs are biocompatible and biodegradable.[2,4]

NPSNPs were prepared via sol-gel process using polystyrene as structure directing agent to build up the porous system.[5] After template removal, the particle surface was modified with different trialkoxysilanes by post-grafting reaction to control siRNA uptake and release. The siRNA-loaded particles were capped with different lipids to enhance cell uptake and siRNA release into the cytoplasm of a cell. The knockdown ability was investigated using siRNA against the green fluorescent protein gene.

The synthesized NPSNPs were approximately 70 nm in size (7 nm pore diameter). By modifying the surface, high loading amounts and an appropriate release could be achieved. Cell uptake investigations and first knockdown experiments showed promising efficiency of our designed inorganic nanocarriers.

[1] Tatiparti et al., Nanomaterials 2017, 7, 77

[2] Möller et al., Nanoscale 2016, 8, 4007

[3] Xue et al., Nanomedicine 2014, 9, 295

[4] Möller et al., Chem.Mater. 2017, 29, 371

[5] Okuyama et al., Microporous Mesoporous Mater. 2009, 120, 447

Karen Besecke
Leibniz University Hannover
Additional Authors:
  • Prof. Dr. Peter Behrens
    Leibniz University Hannover
  • Dr. Philipp Dillschneider
    Hannover Medical School (MHH)
  • Prof. Dr. Meike Stiesch
    Hannover Medical School (MHH)
  • Prof. Dr. Andrea Hoffmann
    Hannover Medical School (MHH)
  • Henning Hartwig
    Hannover Medical School (MHH)