Clusterin in the protein corona plays a key role in the stealth effect of nanoparticles against phagocytes

Clusterin in the protein corona plays a key role in the stealth effect of nanoparticles against phagocytes
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DOI:
10.1016/j.bbrc.2016.10.121
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发表时间:
2016-11-25
影响因子:
3.1
通讯作者:
Tsutsumi, Yasuo
Tsutsumi, Yasuo
中科院分区:
生物学4区
文献类型:
--
作者:
Aoyama, Michihiko;Hata, Katutomo;Tsutsumi, Yasuo

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在生物流体中,纳米颗粒与蛋白质等生物成分相互作用,在纳米颗粒周围形成一层称为“蛋白质冠”的层。据信蛋白质冠的组成影响纳米颗粒的细胞摄取和体内生物分布;然而,控制纳米颗粒生物命运的蛋白质冠的关键蛋白质仍不清楚。最近,有报道称,聚乙二醇化纳米颗粒与簇蛋白的结合对于聚乙二醇化纳米颗粒在吞噬细胞中的隐形效应是重要的。然而,聚集蛋白对非聚乙二醇化纳米颗粒的影响是未知的,尽管已知聚集蛋白存在于非聚乙二醇化纳米颗粒的蛋白质冠中。在这里,我们评估了clusterin在非聚乙二醇化的银纳米颗粒和二氧化硅纳米颗粒的冠中的隐形效应。我们发现,血清和血浆蛋白冠抑制吞噬细胞的银纳米粒子和二氧化硅纳米粒子的细胞摄取,血浆蛋白冠显示出更大的隐形效果相比,血清蛋白冠。在血清和血浆蛋白质冠中均存在白藜芦醇,但血浆蛋白质冠中的白藜芦醇水平高于血清蛋白质冠。与银纳米颗粒和二氧化硅纳米颗粒结合的白藜芦醇抑制了人巨噬细胞样细胞(THP-1细胞)中纳米颗粒的细胞摄取。虽然还需要进一步的研究来确定clusterin如何抑制吞噬细胞的非特异性细胞摄取,但我们的数据表明clusterin不仅在聚乙二醇化纳米颗粒而且在非聚乙二醇化纳米颗粒的隐形效应中起着关键作用。(C)2016 Elsevier Inc. All rights reserved.
In biological fluids, nanoparticles interact with biological components such as proteins, and a layer called the "protein corona" forms around the nanoparticles. It is believed that the composition of the protein corona affects the cellular uptake and in vivo biodistribution of nanoparticles; however, the key proteins of the protein corona that control the biological fate of nanoparticles remain unclear. Recently, it was reported that clusterin binding to pegylated nanoparticles is important for the stealth effect of pegylated nanoparticles in phagocytes. However, the effect of clusterin on non-pegylated nanoparticles is unknown, although it is known that clusterin is present in the protein corona of non-pegylated nano particles. Here, we assessed the stealth effect of clusterin in the corona of non-pegylated silver nanoparticles and silica nanoparticles. We found that serum-and plasma-protein corona inhibited the cellular uptake of silver nanoparticles and silica nanoparticles in phagocytes and that the plasma-protein corona showed a greater stealth effect compared with the serum-protein corona. Clusterin was present in both the serum-and plasma-protein corona, but was present at a higher level in the plasma-protein corona than in the serum-protein corona. Clusterin binding to silver nanoparticles and silica nano particles suppressed the cellular uptake of nanoparticles in human macrophage-like cells (THP-1 cells). Although further studies are required to determine how clusterin suppresses non-specific cellular uptake in phagocytes, our data suggest that clusterin plays a key role in the stealth effect of not only pegylated nanoparticles but also non-pegylated nanoparticles. (C) 2016 Elsevier Inc. All rights reserved.