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

• Published in: Journal of biomedical materials research. Part A Vol. 103; no. 5; pp. 1622 - 1631
• Main Authors: Wardwell, Patricia R., Bader, Rebecca A.
• Format: Journal Article
• Language: English
• Published: United States 01-05-2015
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Cell Line; Chitosan; Chitosan - chemistry; Coated Materials, Biocompatible - chemistry; Coating; Cystic fibrosis; Cystic Fibrosis - pathology; Decoys; Diseases; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - drug effects; Epithelial Cells - immunology; Genes, Reporter; Humans; immunomodulation; Immunomodulation - drug effects; Interleukin; Interleukin-6 - secretion; Interleukin-8 - secretion; Luciferases - metabolism; Nanoparticles; Nanoparticles - chemistry; NF-kappa B - metabolism; NF‐κB; Oligodeoxyribonucleotides - pharmacology; oligonucleotides; Polysaccharides - chemistry; Pseudomonas aeruginosa; Rats; Secretions; Sialic Acids - chemistry; Signal Transduction - drug effects; NF-κB; immunomodulation; nanoparticles; oligonucleotides; cystic fibrosis
• ISSN: 1549-3296; 1552-4965
• DOI: 10.1002/jbm.a.35296

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. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1622–1631, 2015.