+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Enhanced cellular uptake and gene silencing activity of siRNA molecules mediated by chitosan-derivative nanocomplexes



Enhanced cellular uptake and gene silencing activity of siRNA molecules mediated by chitosan-derivative nanocomplexes



International Journal of Pharmaceutics 473(1-2): 579-590



The RNA interference (RNAi) constitutes a conservative mechanism in eukaryotic cells that induces silencing of target genes. In mammalians, the RNAi is triggered by siRNA (small interfering RNA) molecules. Due to its potential in silencing specific genes, the siRNA has been considered a potential alternative for the treatment of genetic and acquired diseases. However, the siRNA therapy has been limited by its low stability and rapid degradation in presence of nucleases, low cellular uptake, and immune response activation. In order to overcome these drawbacks, we propose the synthesis and characterization of non-viral delivery systems using chitosan derivatives to obtain siRNA complexes (polyplexes). The non-viral delivery systems synthesized included PEG-g-OCs (oligochitosan) and PEG-g-Cs (chitosan medium molecular weight). Both systems allowed the formation of siRNA polyplexes, increased the stability of siRNA in the presence of nucleases, enhanced cellular internalization, and showed low toxicity in the A549 cell line. Finally, the complexes obtained with the PEG-g-OCs system showed silencing activity in a GFP model in the cell line A549 in comparison with naked siRNA.

(PDF emailed within 0-6 h: $19.90)

Accession: 052982683

Download citation: RISBibTeXText

PMID: 25063077

DOI: 10.1016/j.ijpharm.2014.07.026


Related references

Functional gene silencing mediated by chitosan/siRNA nanocomplexes. Nanotechnology 20(40): 405103-405103, 2009

Enhanced cellular uptake and gene silencing activity of siRNA using temperature-responsive polymer-modified liposome. International Journal of Pharmaceutics 523(1): 217-228, 2017

Chitosanase-based method for RNA isolation from cells transfected with chitosan/siRNA nanocomplexes for real-time RT-PCR in gene silencing. International Journal of Nanomedicine 5: 473-481, 2011

Enhancement of efficiencies of the cellular uptake and gene silencing of chitosan/siRNA complexes via the inclusion of a negatively charged poly(γ-glutamic acid). Biomaterials 31(33): 8780-8788, 2011

Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing. Theranostics 4(10): 1039-1051, 2015

Stability and cellular uptake of polymerized siRNA (poly-siRNA)/polyethylenimine (PEI) complexes for efficient gene silencing. Journal of Controlled Release 141(3): 339-346, 2010

Functional TNFα gene silencing mediated by polyethyleneimine/TNFα siRNA nanocomplexes in inflamed colon. Biomaterials 32(4): 1218-1228, 2011

Disulfide-based poly(amido amine)s for siRNA delivery: effects of structure on siRNA complexation, cellular uptake, gene silencing and toxicity. Pharmaceutical Research 28(5): 1013-1022, 2011

Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group. Nucleic Acids Research 40(5): 2330-2344, 2012

Gene silencing activity of siRNA polyplexes based on thiolated N,N,N-trimethylated chitosan. Bioconjugate Chemistry 21(12): 2339-2346, 2011

Reducible siRNA dimeric conjugates for efficient cellular uptake and gene silencing. Bioconjugate Chemistry 22(2): 299-306, 2011

Photochemical internalization (PCI)-mediated enhancement of gene silencing efficiency of polymethacrylates and N,N,N-trimethylated chitosan (TMC) based siRNA polyplexes. Journal of Controlled Release 148(1): E98-E99, 2011

Mechanisms of cellular uptake and endosomal escape of calcium-siRNA nanocomplexes. International Journal of Pharmaceutics 515(1-2): 46-56, 2016

Quaternized starch-based carrier for siRNA delivery: from cellular uptake to gene silencing. Journal of Controlled Release 185: 109-120, 2015

Gene silencing activity of siRNA molecules containing phosphorodithioate substitutions. Acs Chemical Biology 7(7): 1214-1220, 2013