Synthetic vaccine nanoparticles target to lymph node triggering enhanced innate and adaptive antitumor immunity Sohyun Kim1, Hathaichanok Phuengkham1, Sun-Young Kim1, Yong Taik Lim1* 1SKKU Advanced Institute of Nanotechnology (SAINT) and School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea
Here, synthetic vaccine nanoparticles (SVNPs) efficiently targeting to lymph nodes where the immune responses against foreign antigens are primed, were developed to enhance antitumor immunity. The size (20-70 nm) and surface character (amination) of SVNPs based on poly(-glutamic acid) were tuned for the effective loading and targeting (i.e., migration and retention) of model tumor antigen (OVA) and toll-like receptor 3 agonist (poly(I:C)) to the immune cells in lymph nodes. The uptake of OVA and poly (I:C) and the secretion of inflammatory cytokines (TNF-α, IL-6) and type I interferon (IFN-α, IFN-β) by antigen-presenting cells treated with SVNP-OVA and SVNP-IC were higher than those following treatment with OVA and poly(I:C) alone. In vivo analysis of activation markers, inflammatory cytokines and type I interferon in the lymph node revealed higher level in mice immunized with SVNP-IC compared to other groups. In vivo natural killer cell expansion/activation (NK1.1+ cells) and the CD8+ T cell response (CD8+ INF-γ+ cells) in innate and adaptive immunity, respectively, were significantly high in SVNP-IC-treated mice. For EG7-OVA tumor bearing mice, the simultaneous injection of both SVNP-OVA and SVNP-IC induced higher antitumor immunity and inhibited tumor growth both in preventive and therapeutic vaccination.
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