Synthetic vaccine nanoparticles target to lymph node triggering enhanced innate and adaptive antitumor immunity.

ABSTRACT

In this study, synthetic vaccine nanoparticles (SVNPs) that efficiently targeted lymph nodes, where immune responses against foreign antigens are primed, were developed to enhance antitumor immunity. The size (20-70 nm) and surface character (amination) of poly(γ-glutamic acid)-based SVNPs were selected for effective loading and delivery (i.e., migration and retention) of model tumor antigen (OVA) and toll-like receptor 3 agonist (poly (IC)) to immune cells in lymph nodes. Antigen-presenting cells treated with SVNP-OVA and SVNP-IC showed higher uptake of OVA and poly (IC) and higher secretion of inflammatory cytokines (TNF-α, IL-6) and type I interferon (IFN-α, IFN-ß) than those treated with OVA and poly (IC) alone. In vivo analysis revealed higher levels of activation markers, inflammatory cytokines, and type I IFNs in the lymph nodes of mice immunized with SVNP-IC compared to those of mice in other groups. SVNP-IC-treated mice showed significantly greater in vivo natural killer cell expansion/activation (NK1.1+ cells) and CD8+ T cell response (CD8+ INF-γ+ cells) in innate and adaptive immunity, respectively. Both preventive and therapeutic vaccination of EG7-OVA tumor-bearing mice using the simultaneous injection of both SVNP-OVA and SVNP-IC induced higher antitumor immunity and inhibited tumor growth.