Proinflammatory Effects of Pyrogenic and Precipitated Amorphous Silica Nanoparticles in Innate Immunity Cells
Proinflammatory Effects of Pyrogenic and Precipitated Amorphous Silica Nanoparticles in Innate Immunity Cells
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DOI：
10.1093/toxsci/kfv258
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发表时间：
2016-03-01
影响因子：
3.8
通讯作者：
Bergamaschi, Enrico
中科院分区：
文献类型：
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作者：
Di Cristo, Luisana;Movia, Dania;Bergamaschi, Enrico
无定形二氧化硅纳米颗粒（ASNP）可以通过几种方法合成，其中2种是热路线（以产生热解二氧化硅）和从含有硅酸盐的溶液的湿路线（以获得沉淀的、胶体的、中孔二氧化硅或硅胶）。这两种合成方法都产生了用作食品添加剂（E551）的ASNP。目前的食品法规并不要求在产品标签上注明添加剂的生产方法，因此，ASNP在列出时没有提及生产方法。然而，最近的结果表明，热原ASNP比通过湿法合成的ASNP更具细胞毒性。本研究旨在澄清在完全生长培养基中具有可比尺寸、比表面积、表面电荷和流体动力学半径的2种ASNP代表性制剂NM-203（热原）和NM-200（沉淀）是否对2种小鼠巨噬细胞系（MH-S和RAW264.7细胞）具有不同的影响。我们的研究结果表明，当在富含蛋白质的液体中孵育时，NM-203比NM-200在其表面上吸附更多的蛋白质，并且一旦与巨噬细胞孵育，就会引起更大的氧化应激，从Hmox 1诱导和ROS产生进行评估。流式细胞术和氦离子显微镜表明，热原NM-203与巨噬细胞的相互作用比沉淀NM-200更强烈，并引发了更明显的炎症反应，与Nos 2诱导，NO产生和TNF-α，IL-6和IL-1 β的分泌进行了评估。此外，两种ASNP都协同细菌脂多糖（LPS）对巨噬细胞的激活，其中对于NM-203观察到更高的效果。综上所述，本研究结果表明，与沉淀相比，热原ASNP与血清蛋白和细胞膜的相互作用增强，并在巨噬细胞中引起更大的氧化应激和更强的促炎作用。因此，这2种纳米材料不应视为生物等效。
Amorphous silica nanoparticles (ASNP) can be synthetized via several processes, 2 of which are the thermal route (to yield pyrogenic silica) and the wet route from a solution containing silicate salts (to obtain precipitated, colloidal, mesoporous silica, or silica gel). Both methods of synthesis lead to ASNP that are applied as food additive (E551). Current food regulation does not require that production methods of additives are indicated on the product label, and, thus, the ASNP are listed without mentioning the production method. Recent results indicate, however, that pyrogenic ASNP are more cytotoxic than ASNP synthesized through the wet route. The present study was aimed at clarifying if 2 representative preparations of ASNP, NM-203 (pyrogenic) and NM-200 (precipitated), of comparable size, specific surface area, surface charge, and hydrodynamic radius in complete growth medium, had different effects on 2 murine macrophage cell lines (MH-S and RAW264.7 cells). Our results show that, when incubated in protein-rich fluids, NM-203 adsorbed on their surface more proteins than NM-200 and, once incubated with macrophages, elicited a greater oxidative stress, assessed from Hmox1 induction and ROS production. Flow cytometry and helium ion microscopy indicated that pyrogenic NM-203 interacted with macrophages more strongly than the precipitated NM-200 and triggered a more evident inflammatory response, evaluated with Nos2 induction, NO production and the secretion of TNF-alpha, IL-6 and IL-1 beta. Moreover, both ASNP synergized macrophage activation by bacterial lipopolysaccharide (LPS), with a higher effect observed for NM-203. In conclusion, the results presented here demonstrate that, compared to precipitated, pyrogenic ASNP exhibit enhanced interaction with serum proteins and cell membrane, and cause a larger oxidative stress and stronger proinflammatory effects in macrophages. Therefore, these 2 nanomaterials should not be considered biologically equivalent.