Synthesis of TLR7 Agonists Conjugated Iron Oxide Nanoparticles to Elicit Robust Cytotoxic T Cell Responses via DC Activation
홍성유* 김우겸1
UNIST 나노생명화학공학부 1UNIST 화학공학과
발표분야: 생명화학
발표형식: 포스터
발표코드: BIO.P-320
발표회장: P
발표일시: 금 13:00~14:30
Recognitionis of pathogen-associated molecular patterns (PAMPs) is the first steps in immune therapy. Especially, Toll-like receptors (TLRs) in dendritic cell (DC) are representative pattern recognition receptors, which is critical for coordinating innate and adaptive immune responses. Imidazoquinolines, known as artificial compounds commerically available as TLR7 agonists, were attacked in aspect of efficiency because of their small size and short half-life in the bloodstream. Here, we synthesized covalent incorporation of imidazoquinoline moieties onto the surface of iron oxide nanoparticles to enhance their chemical stability, cellular uptake efficiency, and adjuvanticity. We utilized copper-catalyzed click reaction (CuAAC) to make novel conjugation between adjuvant and nanoparticles and these synthetic adjuvant-nanocomplexes showed powerful DC activation with lower nanomolar doses. Furthermore we checked unusually strong cytotoxic T lymphocyte responses, by the addition of ovalbumin, because conjugation to macromolecules could induce multivalency effect and efficient transport to endosomal TLR7.
