High content analysis provides mechanistic insights on the pathways of toxicity induced by amine-modified polystyrene nanoparticles.
High content analysis provides mechanistic insights on the pathways of toxicity induced by amine-modified polystyrene nanoparticles.
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DOI：
10.1371/journal.pone.0108025
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Dawson KA
中科院分区：
文献类型：
--
作者：
Anguissola S;Garry D;Salvati A;O'Brien PJ;Dawson KA
纳米技术的快速发展需要有效的安全检测作为支撑。我们已经开发了一个筛选平台，同时测量暴露于不同浓度的纳米颗粒（NPs）的几个细胞参数。不同器官细胞类型的细胞系，包括肺、内皮、肝、肾、巨噬细胞、胶质细胞和神经元细胞，暴露于50 nm的胺修饰聚苯乙烯（PS-NH2） NPs中，此前有报道称其可诱导细胞凋亡，50 nm的磺化和羧基修饰聚苯乙烯NPs则被报道为沉默。除Raw 264.7外，所有细胞系均对PS-NH2 NPs产生凋亡反应，显示出特定的EC50阈值序列；溶酶体酸化是最敏感的参数。高含量分析测量的线粒体膜电位和质膜完整性损失与经合组织推荐的等效测定方法相当敏感，从而增加了产量。酸性区室分析显示，PS-NH2 NPs的大小/荧光强度与应用剂量具有良好的相关性；此外，还观察到脂肪变性和磷脂变性，这与溶酶体绿色显示的溶酶体改变一致；在比较星形细胞瘤细胞和原代星形细胞时，观察到类似的反应。我们已经建立了一个平台，提供了对纳米颗粒暴露反应的机制见解。该平台在体外高通量筛选纳米材料方面具有很大的潜力。
The fast-paced development of nanotechnology needs the support of effective safety testing. We have developed a screening platform measuring simultaneously several cellular parameters for exposure to various concentrations of nanoparticles (NPs). Cell lines representative of different organ cell types, including lung, endothelium, liver, kidney, macrophages, glia, and neuronal cells were exposed to 50 nm amine-modified polystyrene (PS-NH2) NPs previously reported to induce apoptosis and to 50 nm sulphonated and carboxyl-modified polystyrene NPs that were reported to be silent. All cell lines apart from Raw 264.7 executed apoptosis in response to PS-NH2 NPs, showing specific sequences of EC50 thresholds; lysosomal acidification was the most sensitive parameter. Loss of mitochondrial membrane potential and plasma membrane integrity measured by High Content Analysis resulted comparably sensitive to the equivalent OECD-recommended assays, allowing increased output. Analysis of the acidic compartments revealed good cerrelation between size/fluorescence intensity and dose of PS-NH2 NPs applied; moreover steatosis and phospholipidosis were observed, consistent with the lysosomal alterations revealed by Lysotracker green; similar responses were observed when comparing astrocytoma cells with primary astrocytes. We have established a platform providing mechanistic insights on the response to exposure to nanoparticles. Such platform holds great potential for in vitro screening of nanomaterials in highthroughput format.
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影响因子：
13.3
作者：
dos Santos, Tiago;Varela, Juan;Dawson, Kenneth A.
通讯作者：
Dawson, Kenneth A.
影响因子：
17.1
作者：
Jan, Edward;Byrne, Stephen J.;Kotov, Nicholas A.
通讯作者：
Kotov, Nicholas A.
影响因子：
17.1
作者：
Kim, Jong Ah;Aberg, Christoffer;Dawson, Kenneth A.
通讯作者：
Dawson, Kenneth A.
DOI：
10.1016/0005-2760(79)90132-2
发表时间：
1979-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
BUCHHEIM, W;DRENCKHAHN, D;LULLMANNRAUCH, R
通讯作者：
LULLMANNRAUCH, R
影响因子：
17.1
作者：
Lunov, Oleg;Syrovets, Tatiana;Simmet, Thomas
通讯作者：
Simmet, Thomas