title: Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles.
abstract: Modulation of immune response is important in cancer immunotherapy, vaccine adjuvant development and inflammatory or immune disease therapy. Here we report the development of new immunomodulators via control of shape transition among RNA triangle, square and pentagon. 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. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-α and IL-6 induction was greatly enhanced in vitro and in animals up to 100-fold, while RNA polygon controls induced unnoticeable effect. The RNA nanoparticles were delivered to macrophages specifically. 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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Emil F
authors.initials: EF
authors.lastname: Khisamutdinov
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Jasinski
authors.affiliation: Center for Research on Environmental Disease, Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center for Research on Environmental Disease, Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky, Lexington, KY 40536, USA peixuan.guo@uky.edu.
authors.forename: Peixuan
authors.initials: P
authors.lastname: Guo
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004337:Drug Carriers / Q000737:chemistry*; D007113:Immunity, Innate / Q000187:drug effects*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D059372:Nucleotide Motifs; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D012313:RNA / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D004337:Drug Carriers; D009838:Oligodeoxyribonucleotides; D012313:RNA
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