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Nanoparticle geometry and surface orientation influence mode of cellular uptake

机译:纳米粒子的几何形状和表面取向影响细胞摄取的方式

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In order to engineer safer nanomaterials, there is a need to understand, systematically evaluate, and develop constructs with appropriate cellular uptake and intracellular fates. The overall goal of this project is to determine the uptake patterns of silica nanoparticle geometries in model cells, in order to aid in the identification of the role of geometry on cellular uptake and transport. In our experiments we observed a significant difference in the viability of two phenotypes of primary macrophages; immortalized macrophages exhibited similar patterns. However, both primary and immortalized epithelial cells did not exhibit toxicity profiles. Interestingly uptake of these geometries in all cell lines exhibited very different time-dependent patterns. A screening of a series of chemical inhibitors of endocytosis was performed to isolate the uptake mechanisms of the different particles. The results show that all geometries exhibit very different uptake profiles and that this may be due to the orientation of the nanoparticles when they interact with the cell surface. Additionally, evidence suggests that these uptake patterns initialize different downstream cellular pathways, dependent on cell type and phenotype.
机译:为了工程设计更安全的纳米材料,需要了解,系统地评估和开发具有适当细胞摄取和细胞内命运的构建体。该项目的总体目标是确定模型细胞中二氧化硅纳米颗粒几何形状的摄取模式,以帮助确定几何形状对细胞摄取和运输的作用。在我们的实验中,我们观察到了两种主要巨噬细胞表型在活力上的显着差异。永生化的巨噬细胞表现出相似的模式。但是,原代和永生化的上皮细胞均未显示毒性特征。有趣的是,在所有细胞系中这些几何形状的吸收表现出非常不同的时间依赖性模式。进行了一系列内吞作用化学抑制剂的筛选,以分离不同颗粒的摄取机制。结果表明,所有几何形状均表现出截然不同的吸收曲线,这可能是由于纳米粒子在与细胞表面相互作用时的取向所致。另外,有证据表明,这些摄取模式取决于细胞类型和表型而初始化不同的下游细胞途径。

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