title: Covalent Conjugation of Small-Molecule Adjuvants to Nanoparticles Induces Robust Cytotoxic T Cell Responses via DC Activation.
abstract: Specific recognitions of pathogen associated molecular patterns by Toll-like receptors (TLRs) initiate dendritic cell (DC) activation, which is critical for coordinating innate and adaptive immune responses. Imidazoquinolines as small-molecule TLR7 agonists often suffer from prompt dissemination and short half-life in the bloodstream, preventing their localization to the corresponding receptors and effective DC activation. We postulated that covalent incorporation of imidazoquinoline moieties onto the surface of biocompatible nanoparticles (∼30 nm size) would enhance their chemical stability, cellular uptake efficiency, and adjuvanticity. The fully synthetic adjuvant-nanocomplexes led to successful DC activation at lower nanomolar doses compared with free small-molecule agonists. Once a model antigen such as ovalbumin was used for immunization, we found that the nanocomplexes promoted an unusually strong cytotoxic T lymphocyte response, revealing their unique immunostimulatory capacity benefiting from multivalency and efficient transport to endosomal TLR7.
authors: School of Energy and Chemical Engineering and ‡School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors: Woo Gyum
authors: WG
authors: Kim
authors: School of Energy and Chemical Engineering and ‡School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors: Bongseo
authors: B
authors: Choi
authors: School of Energy and Chemical Engineering and ‡School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors: Hyun-Ji
authors: HJ
authors: Yang
authors: School of Energy and Chemical Engineering and ‡School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors: Jae-A
authors: JA
authors: Han
authors: School of Energy and Chemical Engineering and ‡School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors: Hoesu
authors: H
authors: Jung
authors: School of Energy and Chemical Engineering and ‡School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors: HyungJoon
authors: H
authors: Cho
authors: School of Energy and Chemical Engineering and ‡School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors: Sebyung
authors: S
authors: Kang
authors: School of Energy and Chemical Engineering and ‡School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors: Sung You
authors: SY
authors: Hong
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D053758:Nanoparticles / Q000737:chemistry*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic