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: Previously, it has been demonstrated that the CpG oligonucleotide can be readily recognized by TLR9 on the endosomal membrane of macrophages, resulting in cellular uptake of the CpG adjuvants (58,59). To investigate whether there is a difference between the efficiency of RNA polygons binding to the cells, we quantified the cellular uptake of polygons-CpG using flow cytometry assay (9,10). Figure 6A demonstrates the binding of different RNA polygon-CpG to the RAW264.7 cells in a dose-dependent manner. There was an increase in binding efficiency from triangle to pentagon with more CpGs (Supplementary Figure S8). Notably, all RNA polygons-CpG complexes remain intact after 16 h incubation in 10% fetal bovine serum (FBS) indicating robustness of the assembled complex in extracellular environment (Supplementary Figure S9). Overall, RNA polygon-CpG complexes exhibit significantly more binding efficiency to cells compared to CpG oligonucleotides alone.
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky, Lexington, KY 40536, USA.