Download Size effect of spherical gold nanoparticles on lymph node

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.