Iron oxide nanoparticle agglomeration influences dose rates and modulates oxidative stress-mediated dose-response profiles in vitro.
Iron oxide nanoparticle agglomeration influences dose rates and modulates oxidative stress-mediated dose-response profiles in vitro.
复制标题
DOI：
10.3109/17435390.2013.822115
复制
发表时间：
2014-09
期刊：
影响因子：
5
通讯作者：
Thrall BD
中科院分区：
文献类型：
--
作者：
Sharma G;Kodali V;Gaffrey M;Wang W;Minard KR;Karin NJ;Teeguarden JG;Thrall BD
工程纳米粒子（ENP）的自发团聚是细胞培养基中的一个常见问题，它可能会混淆体外纳米毒性研究的解释。作者在传统培养基中创建了稳定的氧化铁纳米粒子 (IONP) 团聚物，其流体动力学尺寸各异 (276 nm–1.5 μm)，但由具有相似表面电位和蛋白质涂层的相同初级粒子组成。使用 C10 肺上皮细胞的研究表明，团聚的剂量率影响可能很大，在某些情况下，细胞剂量的差异超过一个数量级。磁性粒子检测定量表明，在相同的总细胞IONP质量剂量基础上，与大团聚体相比，羧化IONP的小团聚体诱导更大的细胞毒性和氧化还原调节的基因表达，而胺修饰的IONPs的团聚体未能诱导细胞毒性或氧化还原调节的基因表达，尽管传递了相似的细胞剂量。剂量测定模型和实验测量表明，在所提供的表面积的基础上，羧化IONP的大小团聚体在产生ROS、诱导应激相关基因和最终的细胞毒性方面具有相似的内在效力。结果表明，团聚体表面上的反应部分比埋在团聚体核心内的分子更能有效地催化细胞 ROS 的产生。由于 ENP 体外递送至细胞的动态、大小和密度依赖性，仅通过暴露浓度 (μg/ml) 的静态测量无法辨别团聚的生物学后果，这凸显了综合物理表征和定量剂量测定对于体外研究的核心重要性。实验和计算相结合的方法为评估纳米颗粒的生物相容性与其物理和化学特性之间的关系提供了一个定量框架。
Spontaneous agglomeration of engineered nanoparticles (ENPs) is a common problem in cell culture media which can confound interpretation of in vitro nanotoxicity studies. The authors created stable agglomerates of iron oxide nanoparticles (IONPs) in conventional culture medium, which varied in hydrodynamic size (276 nm–1.5 μm) but were composed of identical primary particles with similar surface potentials and protein coatings. Studies using C10 lung epithelial cells show that the dose rate effects of agglomeration can be substantial, varying by over an order of magnitude difference in cellular dose in some cases. Quantification by magnetic particle detection showed that small agglomerates of carboxylated IONPs induced greater cytotoxicity and redox-regulated gene expression when compared with large agglomerates on an equivalent total cellular IONP mass dose basis, whereas agglomerates of amine-modified IONPs failed to induce cytotoxicity or redox-regulated gene expression despite delivery of similar cellular doses. Dosimetry modelling and experimental measurements reveal that on a delivered surface area basis, large and small agglomerates of carboxylated IONPs have similar inherent potency for the generation of ROS, induction of stress-related genes and eventual cytotoxicity. The results suggest that reactive moieties on the agglomerate surface are more efficient in catalysing cellular ROS production than molecules buried within the agglomerate core. Because of the dynamic, size and density-dependent nature of ENP delivery to cells in vitro, the biological consequences of agglomeration are not discernible from static measures of exposure concentration (μg/ml) alone, highlighting the central importance of integrated physical characterisation and quantitative dosimetry for in vitro studies. The combined experimental and computational approach provides a quantitative framework for evaluating relationships between the biocompatibility of nanoparticles and their physical and chemical characteristics.
登录
查看更多内容
影响因子：
10
作者：
Hinderliter PM;Minard KR;Orr G;Chrisler WB;Thrall BD;Pounds JG;Teeguarden JG
通讯作者：
Teeguarden JG
影响因子：
--
作者：
Mahl, Dirk;Greulich, Christina;Epple, Matthias
通讯作者：
Epple, Matthias
影响因子：
5
作者：
Cohen J;Deloid G;Pyrgiotakis G;Demokritou P
通讯作者：
Demokritou P
影响因子：
17.1
作者：
Albanese, Alexandre;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.
影响因子：
3.8
作者：
Ferguson, R. Matthew;Minard, Kevin R.;Krishnan, Kannan M.
通讯作者：
Krishnan, Kannan M.