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Min, Junseon,Jung, Hoesu,Shin, Hyun-Hee,Cho, Gyunggoo,Cho, HyungJoon,Kang, Sebyung American Chemical Society 2013 Biomacromolecules Vol.14 No.7
<P>P22 viral capsids and ferritin protein cages are utilized as templating macromolecules to conjugate Gd(III)-chelating agent complexes, and we systematically investigates the effects of the macromolecules’ size and the conjugation positions of Gd(III)-chelating agents on the magnetic resonance (MR) relaxivities and the resulting image contrasts. The relaxivity values of the Gd(III)-chelating agent-conjugated P22 viral capsids (outer diameter: 64 nm) are dramatically increased as compared to both free Gd(III)-chelating agents and Gd(III)-chelating agent-conjugated ferritins (outer diameter: 12 nm), suggesting that the large sized P22 viral capsids exhibit a much slower tumbling rate, which results in a faster <I>T</I><SUB>1</SUB> relaxation rate. Gd(III)-chelating agents are attached to either the interior or exterior surface of P22 viral capsids and the conjugation positions of Gd(III)-chelating agents, however, do not have a significant effect on the relaxivity values of the macromolecular conjugates. The contrast enhancement of Gd(III)-chelating agent-conjugated P22 viral capsids is confirmed by in vitro phantom imaging at a short repetition times (TR) and the potential usage of Gd(III)-chelating agent-conjugated P22 viral capsids for in vivo MR imaging is validated by visualizing a mouse’s intravascular system, including the carotid, mammary arteries, the jugular vein, and the superficial vessels of the head at an isotropic resolution of 250 μm.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2013/bomaf6.2013.14.issue-7/bm400461j/production/images/medium/bm-2013-00461j_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bm400461j'>ACS Electronic Supporting Info</A></P>
Kim, Woo Gyum,Choi, Bongseo,Yang, Hyun-Ji,Han, Jae-A,Jung, Hoesu,Cho, HyungJoon,Kang, Sebyung,Hong, Sung You American Chemical Society 2016 Bioconjugate chemistry Vol.27 No.9
<P>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 (similar to 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.</P>