Immunomodulation of cystic fibrosis epithelial cells via NF-[kappa]B decoy oligonucleotide-coated polysaccharide nanoparticles

• Published in: Journal of biomedical materials research. Part A Vol. 103; no. 5; p. 1622
• Main Authors: Wardwell, Patricia R, Bader, Rebecca A
• Format: Journal Article
• Language: English
• Published: Mount Laurel Wiley Subscription Services, Inc 01-05-2015
• ISSN: 1549-3296; 1552-4965
• DOI: 10.1002/jbm.a.35296

Activation of the transcription factor nuclear factor-kappa B (NF-[kappa]B) 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-[kappa][Beta] 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-1[beta] 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-[kappa]B decoy ODN-coated TMC-PSA nanoparticles may serve as an effective method of altering the pro-inflammatory environment associated with CF. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1622-1631, 2015.