Journal
NUCLEIC ACIDS RESEARCH
Volume 42, Issue 15, Pages 9996-10004Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gku516
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Funding
- NIH grant, National Institute of Biomedical Imaging and Engineering [R01-EB003730]
- National Cancer institute [U01-CA 151648]
- William Fairish Endowment Fund
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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 degrees to 90 degrees or 108 degrees, resulting in self-assembly of elegant RNA triangles, squares and pentagons. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-alpha 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.
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