Gold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses in Vitro and in Vivo
Gold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses in Vitro and in Vivo
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DOI：
10.1021/nn3057005
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发表时间：
2013-05-01
期刊：
影响因子：
17.1
通讯作者：
Sawa, Hirofumi
中科院分区：
文献类型：
--
作者：
Niikura, Kenichi;Matsunaga, Tatsuya;Sawa, Hirofumi
本文介绍了金纳米粒子(AuNPs)的形状和大小对体内和体外产生西尼罗河病毒抗体的免疫应答的影响。我们制备了球形(直径20 nm和40 nm)、棒状(40×10 nm)和立方体(40×40×40 nm)AuNPs作为佐剂，并将其包裹在WNV包膜蛋白(E)上。我们检测了这些包被WNVE的AuNPs(AuNP-ES)接种小鼠后产生的抗WNVE抗体。40 nm球形AuNP-ES(Sphere40-ES)诱导的WNVE特异性抗体水平最高，而杆状AuNP-ES(Rod-ES)诱导的抗体水平仅为Sphere40-E的50%。为了研究形状依赖的WNVE抗体产生的机制，我们接下来测量了RAW264.7巨噬细胞和骨髓来源的树突状细胞(BMDCs)对AuNP-ES的细胞摄取效率以及随后BMDCs分泌的细胞因子。Rod-ES对细胞的摄取比球形ES或立方体WNVE包被AuNPs(CuBE-ES)更有效，这表明抗体的产生不依赖于不同AuNP-ES的摄取效率。经AuNP-ES处理的BMDCs产生的细胞因子显示，只有Rod-E处理的细胞产生显著水平的IL-1β(IL-1β)和IL-18(IL-18)，这表明Rod-ES激活了炎症体依赖的细胞因子的分泌。同时，Sphere40-ES和Cube-ES均显著诱导炎性细胞因子的产生，包括肿瘤坏死因子-α(TNF-α)、IL-6、IL-12和粒细胞-巨噬细胞集落刺激因子(GM-CSF)。这些结果表明，AuNPs是有效的疫苗佐剂，根据其大小和形状的不同，通过不同的细胞因子途径增强免疫应答。
This paper demonstrates how the shape and size of gold nanoparticles (AuNPs) affect immunological responses in vivo and in vitro for the production of antibodies for West Nile virus (WNV). We prepared spherical (20 and 40 nm in diameter), rod (40 x 10 nm), and cubic (40 x 40 x 40 nm) AuNPs as adjuvants and coated them with WNV envelope (E) protein. We measured anti-WNVE antibodies after inoculation of these WNVE-coated AuNPs (AuNP-Es) into mice. The 40 nm spherical AuNP-Es (Sphere40-Es) induced the highest level of WNVE-specific antibodies, while rod AuNP-Es (Rod-Es) induced only 50% of that of Sphere40-E. To examine the mechanisms of the shape-dependent WNVE antibody production, we next measured the efficiency of cellular uptake of AuNP-Es into RAW264.7 macrophage cells and bone-marrow-derived dendritic cells (BMDCs) and the subsequent cytokine secretion from BMDCs. The uptake of Rod-Es into the cells proceeded more efficiently than those of Sphere-Es or cubic WNVE-coated AuNPs (Cube-Es), suggesting that antibody production was not dependent on the uptake efficiency of the different AuNP-Es. Cytokine production from BMDCs treated with the AuNP-Es revealed that only Rod-E-treated cells produced significant levels of interleukin-1 beta (IL-1 beta) and interleukin-18 (IL-18), indicating that Rod-Es activated inflammasome-dependent cytokine secretion. Meanwhile, Sphere40-Es and Cube-Es both significantly induced inflammatory cytokine production, including tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-12, and granulocyte macrophage colony-stimulating factor (GM-CSF). These results suggested that AuNPs are effective vaccine adjuvants and enhance the immune response via different cytokine pathways depending on their sizes and shapes.