Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles.
Bottom Line: Changing one RNA strand in polygons automatically induced the stretching of the interior angle from 60° to 90° or 108°, resulting in self-assembly of elegant RNA triangles, squares and pentagons.The degree of immunostimulation greatly depended on the size, shape and number of the payload per nanoparticles.Stronger immune response was observed when the number of adjuvants per polygon was increased, demonstrating the advantage of shape transition from triangle to pentagon.
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky, Lexington, KY 40536, USA.Show MeSH
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Mentions: The extracellular immunostimulatory efficacy of RNA polygons was evaluated by measuring the release of cytokines TNF-α and IL-6 after addition to mouse macrophage-like RAW 264.7 cells (Figure 5A and B), as previously described (56,57). The triangular RNA nanoparticle coupled with only one CpG exhibited the highest level of cytokine induction for both TNF-α and IL-6 compared to square and pentagonal RNA nanoparticles. Increasing the number of CpG per nanoparticle yielded the opposite effect, as pentagonal RNA nanocarriers showed the highest level of the induction of both TNF-α and IL-6 presumably due to the increased local CpG concentration. The results suggest that the cytokine release by CpG coupled to RNA polygons with different shapes remarkably increases the immunostimulatory activity compared to CpG alone (Figure 5). RNA particles with the size of about 10 nm, such as the triangle, induced the greatest amount of TNF-α and IL-6. In addition, the induction of cytokines was highly dependent on the number of CpG per polygon. With increasing number of CpG per polygon, a stronger immune response is observed (Figure 5C), demonstrating an advantage of transiting from triangle to pentagon that can carry five CpG oligonucleotides.
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky, Lexington, KY 40536, USA.