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Transcript
Size effect of spherical gold nanoparticles on lymph node delivery and T-cell immunity Sukmo Kang†, Jeewon Lee‡, Eui-Cheol Shin‡, Sangyong Jon†‡ † KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea. ‡ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea. Many nanomaterials were recently incorporated into development of vaccines due to their advantages in kinetics of antigen exposure and cellular processing. While physicochemical properties of nanomaterials might be determining factors in the induction of immune response, their ultimate influence on the immune response has not been definitively established and rational vaccine design is challenging. Here, we studied the effect of gold nanoparticle size on lymph node delivery and induction of CD8+ T-cell response. Specifically, immune responses to sub-40nm gold nanoparticles (GNPs) which can directly drain into lymph nodes were assessed. To study the size effect of GNPs on cellular immune response, GNPs with diameters of 7, 14, 28 nm were successfully conjugated with recombinant ovalbumin (OVA-GNPs). DC cell uptake and crosspresentation efficiency in vitro was increased in size-dependently, and lymph node delivery of OVA-GNPs in vivo was higher in 14 and 28 nm of OVA-GNPs compared to 7 nm OVA- GNPs. In ex vivo re-stimulation assay, OVA-GNP (14, 28 nm) immunized groups had higher frequencies of OVA-specific CD8+ T cells, and these cells were proven to be poly-functional compared to OVA-GNP (7 nm)-immunized mice. In tumor prevention study, 14 nm of OVAGNP also showed higher anti-tumor efficacy and induced higher CD8+ T-cell infiltration and apoptotic tumor cell death. Taken together, to develop GNP-based vaccines, more than 14 nm-size of GNP would be the threshold for induction of potent cellular response and T cell poly-functionality. A clear difference of T cell response in narrow size range indicated that even the rather small difference in particle size has significant effect on the retention of nanoparticle in lymph nodes and induction of T-cell response, and highlighted the importance of the size as the critical design parameter in development of nanoparticle-based vaccines.