Regulation of bifurcated cytokine induction by surface charge of nanoparticles during interaction between CpG oligodeoxynucleotides and toll-like receptor 9

Toll-like receptor 9 recognizes CpG oligodeoxynucleotides (ODNs) and induces immune-mediator cytokines. Natural phosphodiester class B CpG ODNs induce interleukin-6 (IL-6), but not interferon-α (IFN-α). We prepared silicon nanoparticles (Si NPs) with different positive surface charge density and bound negatively charged class B CpG ODN molecules electrostatically. No significant differences in the amount of class B CpG ODN molecules or negative surface charge after binding of the molecules onto naked NPs was observed. However, the profile of cytokine induction from peripheral blood mononuclear cells was correlated with a positive surface charge density of naked NPs prior to binding of CpG ODN molecules. The level of IL-6 induction slightly decreased as the positive surface charge density was increased, while the IFN-α induction significantly increased as the positive surface charge density was increased. This observation demonstrates that the bifurcated cytokine induction can be regulated by the surface charge of naked NPs.

Graphical abstractDispersed silicon nanoparticles (Si NPs) with different positive charge densities are used for delivery of immunostimulatory CpG oligodeoxynucleotide (CpG ODN). Free CpG ODN induces interleukin-6 (IL-6), but not interferon-α (IFN-α). However, CpG ODN bound electrostatically onto Si NPs induce not only IL-6, but also IFN-α, at levels that are dependent on the surface charge of the naked Si NPs.Figure optionsDownload full-size imageDownload as PowerPoint slide