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J Biomed Mater Res A. 2015 May;103(5):1622-31. doi: 10.1002/jbm.a.35296. Epub 2014 Aug 14.

Immunomodulation of cystic fibrosis epithelial cells via NF-κB decoy oligonucleotide-coated polysaccharide nanoparticles.

Author information

1
Syracuse Biomaterials Institute, Syracuse University, 318 Bowne Hall, Syracuse, New York, 13244; Department of Biomedical and Chemical Engineering, Syracuse University, 121 Link Hall, Syracuse, New York, 13244.

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.

KEYWORDS:

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

PMID:
25087735
DOI:
10.1002/jbm.a.35296
[Indexed for MEDLINE]

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