Urocanic acid-modified chitosan nanoparticles can confer anti-inflammatory effect by delivering CD98 siRNA to macrophages

• CD98 siRNA (siCD98) was complexed with urocanic acid-modified chitosan (UAC) to form nanoparticles (NPs).
• UAC/siCD98 NPs have no apparent cytotoxicity against Raw 264.7 macrophages and colon-26 cells.
• UAC/siCD98 NPs exhibited a time-dependent cellular uptake profile in Raw 264.7 macrophages.
• UAC/siCD98 NPs with a weight ratio of 60:1 yielded the most efficient knockdowns of CD98 and the pro-inflammatory cytokine (TNF-α).
• The RNAi efficiency of UAC/siCD98 NPs (60:1) was even higher than that of the positive control Oligofectamine/siCD98 NPs.

CD98 plays an important role in the development and progression of inflammation. Here, CD98 siRNA (siCD98) was complexed with urocanic acid-modified chitosan (UAC) to form nanoparticles (NPs), which were transfected into Raw 264.7 macrophages in an effort to convey anti-inflammatory effects. Characterization showed that the generated NPs had a desirable particle size (156.0–247.1 nm), a slightly positive zeta potential (15.8–17.5 mV), and no apparent cytotoxicity against Raw 264.7 macrophages and colon-26 cells compared to control NPs fabricated by Oligofectamine (OF) and siRNA. Cellular uptake experiments demonstrated that macrophages exhibited a time-dependent accumulation profile of UAC/siRNA NPs. Further in vitro gene silencing experiments revealed that UAC/siCD98 NPs with a weight ratio of 60:1 yielded the most efficient knockdowns of CD98 and the pro-inflammatory cytokine, TNF-α. Indeed, the RNAi efficiency obtained with our NPs was even higher than that of the positive control OF/siCD98 NPs. These results suggest that UAC/siCD98 NPs might be a safe, efficient and promising candidate for the treatment of inflammatory disease.

Downregulation of CD98 by urocanic acid-modified chitosan nanoparticles exhibited anti-inflammatory effect.Figure optionsDownload as PowerPoint slide