Microglial Response to Gold Nanoparticles
Microglial Response to Gold Nanoparticles
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DOI：
10.1021/nn901869f
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发表时间：
2010-05-01
期刊：
影响因子：
17.1
通讯作者：
Maysinger, Dusica
中科院分区：
文献类型：
--
作者：
Hutter, Eliza;Boridy, Sebastien;Maysinger, Dusica
鉴于纳米治疗学和纳米诊断学作为当今医学的关键工具的出现，精确定义纳米材料与生物系统的相互作用并表征由此产生的细胞反应变得至关重要。我们在这里报告的相互作用的小胶质细胞和神经元与金纳米粒子（GNP）的三种形态，球，棒，海胆，涂有聚（乙二醇）（PEG）或十六烷基三甲基溴化铵（TAB）。小胶质细胞是大脑的常驻免疫细胞，主要参与监视、巨噬细胞以及细胞因子和营养因子的产生。通过暗视野显微镜和双光子诱导发光（TPL）的分析表明，神经细胞暴露于GNP导致（i）小胶质细胞和原代海马神经元的GNP内化，如通过暗视野显微镜和双光子诱导发光（TPL）所揭示的，（ii）嗅球中的瞬时toll样受体2（TLR-2）上调，在转基因小鼠中鼻内给药后，在体内，在真实的时间，和（iii）TLR-2与白细胞介素1 α（IL-1 α）、粒细胞巨噬细胞集落刺激因子（GM-CSF）和一氧化氮（NO）在小胶质细胞中的体外差异上调。该研究表明，GNP形态和表面化学强烈影响小胶质细胞的活化状态，并表明GNP和小胶质细胞之间的相互作用可以通过调整GNP纳米几何学进行差异调节。
Given the emergence of nanotherapeutics and nanodiagnostics as key tools in today's medicine, it has become of critical importance to define precisely the interactions of nanomaterials with biological systems and to characterize the resulting cellular response. We report here the interactions of microglia and neurons with gold nanoparticles (GNPs) of three morphologies, spheres, rods, and urchins, coated with poly(ethylene glycol) (PEG) or cetyl trimethylammonium bromide ((TAB). Microglia are the resident immune cells of the brain, primarily involved in surveillance, macrophagy, and production of cytokines and trophic factors. Analysis by dark-field microscopy and by two-photon-induced luminescence (TPL) indicates that the exposure of neural cells to GNPs resulted in (i) GNP internalization by both microglial cells and primary hippocampal neurons, as revealed by dark-field microscopy and by two-photon-induced luminescence (TPL), (ii) transient toll-like receptor 2 (TLR-2) up-regulation in the olfactory bulb, after intranasal administration in transgenic mice, in vivo, in real time, and (iii) differential up-regulation in vitro of TLR-2 together with interleukin 1 alpha (IL-1 alpha), granulocyte macrophage colony-stimulating factor (GM-CSF) and nitric oxide (NO) in microglia. The study demonstrates that GNP morphology and surface chemistry strongly influence the microglial activation status and suggests that interactions between GNPs and microglia can be differentially regulated by tuning GNP nanogeometry.