Immunomodulation of cystic fibrosis epithelial cells via NF- κ B decoy oligonucleotide-coated polysaccharide nanoparticles

Patricia R. Wardwell, Rebecca A. Bader

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Activation of the transcription factor nuclear factor-kappa B (NF-κB) signaling pathway is associated with enhanced secretion of pro-inflammatory mediators and is thought to play a critical role in diseases hallmarked by inflammation, including cystic fibrosis (CF). Small nucleic acids that interfere with gene expression have been proposed as promising therapeutics for a number of diseases. However, applications have been limited by low cellular penetration and a lack of stability. Nano-sized carrier systems have been suggested as a means of improving the effectiveness of nucleic acid-based treatments. In this study, we successfully coated polysialic acid-N-trimethyl chitosan (PSA-TMC) nanoparticles with NF-κΒ decoy oligonucleotides (ODNs). To demonstrate anti-inflammatory activity, the decoy ODN-coated PSA-TMC nanoparticles were administered to an in vitro model of CF generated via interleukin-1β or P. aeruginosa lipopolysaccharides stimulation of IB3-1 bronchial epithelial cells. While free ODN and PSA-TMC nanoparticles coated with scrambled ODNs did not have substantial impacts on the inflammatory response, the decoy ODN-coated PSA-TMC nanoparticles were able to reduce the secretion of interleukin-6 and interleukin-8, pro-inflammatory mediators of CF, by the epithelial cells, particularly at longer time points. In general, the results suggest that NF-κB decoy ODN-coated TMC-PSA nanoparticles may serve as an effective method of altering the pro-inflammatory environment associated with CF.

Original languageEnglish (US)
Pages (from-to)1622-1631
Number of pages10
JournalJournal of Biomedical Materials Research - Part A
Volume103
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • NF-κB
  • cystic fibrosis
  • immunomodulation
  • nanoparticles
  • oligonucleotides

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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