Amorphous silica nanoparticles are widely used as pharmaceutical excipients and food additive (E551). Despite the potential human health risks of mineral nanoparticles, very few data regarding their oral toxicity are currently available. This study aims to evaluate and to understand the interactions of silica particles at 1 and 10 mg mL-1 with the intestinal barrier using a Caco-2 monolayer and a Caco-2/HT29-MTX co-culture. A size- and concentration-dependent reversible increase of the paracellular permeability is identified after a short-term exposure to silica nanoparticles. Nanoparticles of 30 nm induce the highest transepithelial electrical resistance drop whereas no effect is observed with 200 nm particles. Additive E551 affect the Caco-2 monolayer permeability. Mucus layer reduces the permeability modulation by limiting the cellular uptake of silica. After nanoparticle exposure, tight junction expression including Zonula occludens 1 (ZO-1) and Claudin 2 is not affected, whereas the actin cytoskeleton disruption of enterocytes and the widening of ZO-1 staining bands are observed. A complete permeability recovery is concomitant with the de novo filament actin assembly and the reduction of ZO-1 bands. These findings suggest the paracellular modulation by small silica particles is directly correlated to the alteration of the ZO-actin binding strongly involved in the stability of the tight junction network.

中文翻译：

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在 Caco-2 和 Caco-2/HT29-MTX 模型中，小的二氧化硅纳米粒子通过肌动蛋白细胞骨架破坏来瞬时调节肠道通透性。

无定形二氧化硅纳米粒子广泛用作药物赋形剂和食品添加剂（E551）。尽管矿物纳米颗粒存在潜在的人类健康风险，但目前很少有关于其口服毒性的数据。本研究旨在使用 Caco-2 单层和 Caco-2/HT29-MTX 共培养物评估和了解 1 和 10 mg mL-1 二氧化硅颗粒与肠道屏障的相互作用。在短期暴露于二氧化硅纳米粒子后，确定了细胞旁通透性的大小和浓度依赖性可逆增加。30 nm 的纳米颗粒诱导最高的跨上皮电阻下降，而 200 nm 颗粒没有观察到影响。添加剂 E551 影响 Caco-2 单层渗透性。粘液层通过限制二氧化硅的细胞摄取来降低渗透性调节。纳米颗粒暴露后，包括 Zonula occludens 1 (ZO-1) 和 Claudin 2 在内的紧密连接表达不受影响，而观察到肠细胞的肌动蛋白细胞骨架破坏和 ZO-1 染色带的加宽。完全的渗透性恢复伴随着从头丝肌动蛋白组装和 ZO-1 带的减少。这些发现表明，小二氧化硅颗粒的细胞旁调节与 ZO-肌动蛋白结合的改变直接相关，这与紧密连接网络的稳定性密切相关。而观察到肠细胞的肌动蛋白细胞骨架破坏和ZO-1染色带的加宽。完全的渗透性恢复伴随着从头丝肌动蛋白组装和 ZO-1 带的减少。这些发现表明，小二氧化硅颗粒的细胞旁调节与 ZO-肌动蛋白结合的改变直接相关，这与紧密连接网络的稳定性密切相关。而观察到肠细胞的肌动蛋白细胞骨架破坏和ZO-1染色带的加宽。完全的渗透性恢复伴随着从头丝肌动蛋白组装和 ZO-1 带的减少。这些发现表明，小二氧化硅颗粒的细胞旁调节与 ZO-肌动蛋白结合的改变直接相关，这与紧密连接网络的稳定性密切相关。