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 (I:C)) to immune cells in lymph nodes. Antigen-presenting cells treated with SVNP-OVA and SVNP-IC showed higher uptake of OVA and poly (I:C) and higher secretion of inflammatory cytokines (TNF-α, IL-6) and type I interferon (IFN-α, IFN-β) than those treated with OVA and poly (I:C) 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.

译文

在这项研究中,开发了有效靶向淋巴结的合成疫苗纳米颗粒 (svnp),以增强抗肿瘤免疫力,在淋巴结中引发针对外来抗原的免疫反应。选择基于聚 (γ-谷氨酸) 的svnp的尺寸 (20-70 nm) 和表面特性 (胺化),以有效加载和递送 (即,模型肿瘤抗原 (OVA) 和toll样受体3激动剂 (poly (I:C)) 向淋巴结免疫细胞的迁移和保留。用SVNP-OVA和SVNP-IC处理的抗原呈递细胞显示出更高的OVA和poly (I:C) 摄取和更高的炎性细胞因子 (TNF-α,IL-6) 和I型干扰素 (IFN-α,IFN-β) 比单独用OVA和poly (I:C) 处理的那些。体内分析显示,与其他组的小鼠相比,用svnp-ic免疫的小鼠淋巴结中的活化标志物,炎性细胞因子和I型ifn水平更高。SVNP-IC处理的小鼠在固有免疫和适应性免疫中分别显示出明显更大的体内自然杀伤细胞扩增/活化 (NK1.1细胞) 和CD8 T细胞反应 (CD8 INF-γ 细胞)。同时注射svnp-ova和svnp-ic对EG7-OVA荷瘤小鼠进行预防和治疗性疫苗接种均诱导更高的抗肿瘤免疫并抑制肿瘤生长。

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