Influence of shape, adhesion and simulated lung mechanics on amorphous silica nanoparticle toxicity
Influence of shape, adhesion and simulated lung mechanics on amorphous silica nanoparticle toxicity
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DOI：
10.1163/156855207779768214
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发表时间：
2007-01-01
影响因子：
5.2
通讯作者：
Moudgil, Brij M.
中科院分区：
文献类型：
--
作者：
Brown, Scott C.;Kamal, Mohammed;Moudgil, Brij M.
流行的理论表明，针状或纤维状颗粒通过阻碍吞噬细胞介导的清除机制和通过机械相互作用加重近端细胞，诱导增强的毒性超过各向同性材料。目前，这两种机制的运作程度还不清楚。为了获得对针状颗粒毒性的更基本的理解，我们合成了亚微米和纳米级无定形二氧化硅球和棒作为形状驱动毒理学实验的模型材料。为了强调体外机械损伤的贡献，在存在和不存在模拟肺力学的情况下进行了暴露研究。为了促进和减轻细胞-颗粒接触介导的机械相互作用，分别通过纤连蛋白的物理吸附和聚乙二醇对二氧化硅颗粒表面的化学吸附来修饰颗粒对细胞膜的粘附。乳酸脱氢酶（LDH）和白细胞介素（IL）-8释放分别用作细胞毒性和炎症的终点。结果表明，在存在生理拉伸的情况下，颗粒暴露诱导LDH释放和IL-8表达增加，而与形状无关。此外，很明显，形状诱导的聚集可能在减轻颗粒清除途径中发挥重要作用。
Prevailing theories suggest that acicular, or fiber-like, particles induce enhanced toxicity over isotropic materials through hindrance of phagocyte-mediated clearance mechanisms and through the aggravation of proximal cells via mechanical interactions. Currently, the degree to which either of these mechanisms operates is not well understood. To gain a more fundamental understanding of acicular particle toxicity, we have synthesized submicron and nanoscale amorphous silica spheres and rods as model materials for shape-driven toxicological experimentation. To accentuate contributions from mechanical damage in vitro, exposure studies were performed in the presence and absence of simulated lung mechanics. To promote and mitigate cell-particle contact-mediated mechanical interactions, the adhesion of the particles to the cell membrane was respectively modified by the physisorption of fibronectin and the chemisorption of polyethylene glycol to the silica particle surface. Lactic acid dehydrogenase (LDH) and interleukin (IL)-8 release were used as endpoints for cytotoxicity and inflammation, respectively. The results indicate that particle exposures in the presence of physiological stretch induce increased LDH release and IL-8 expression regardless of shape. Moreover, it is evident that shape-induced aggregation may play a significant role in mitigating particle clearance pathways.