Ducray Angélique D, Stojiljkovic Ana, Möller Anja, Stoffel Michael H, Widmer Hans-Rudolf, Frenz Martin, Mevissen Meike
Division of Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Division of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Nanomedicine. 2017 Apr;13(3):1195-1204. doi: 10.1016/j.nano.2016.11.001. Epub 2016 Nov 19.
Nanomedicine offers a promising tool for therapies of brain diseases, but they may be associated with potential adverse effects. The aim of this study was to investigate the uptake of silica-nanoparticles engineered for laser-tissue soldering in the brain using SH-SY5Y cells, dissociated and organotypic slice cultures from rat hippocampus. Nanoparticles were predominantly taken up by microglial cells in the hippocampal cultures but nanoparticles were also found in differentiated SH-SY5Y cells. The uptake was time- and concentration-dependent in primary hippocampal cells. Transmission electron microscopy experiments demonstrated nanoparticle aggregates and single particles in the cytoplasm. Nanoparticles were found in the endoplasmic reticulum, but not in other cellular compartments. Nanoparticle exposure did not impair cell viability and neuroinflammation in primary hippocampal cultures at all times investigated. Neurite outgrowth was not significantly altered in SH-SY5Y cells, but the neuronal differentiation markers indicated a reduction in neuronal differentiation induction after nanoparticle exposure.
纳米医学为脑部疾病的治疗提供了一种很有前景的工具,但它们可能会带来潜在的不良影响。本研究的目的是使用SH-SY5Y细胞、大鼠海马体解离细胞和器官型切片培养物,研究用于激光组织焊接的二氧化硅纳米颗粒在脑中的摄取情况。纳米颗粒主要被海马体培养物中的小胶质细胞摄取,但在分化的SH-SY5Y细胞中也发现了纳米颗粒。在原代海马体细胞中,摄取呈时间和浓度依赖性。透射电子显微镜实验证明,纳米颗粒聚集体和单个颗粒存在于细胞质中。在内质网中发现了纳米颗粒,但在其他细胞区室中未发现。在所有研究时间点,纳米颗粒暴露均未损害原代海马体培养物中的细胞活力和神经炎症。纳米颗粒暴露后,SH-SY5Y细胞中的神经突生长没有显著改变,但神经元分化标志物表明纳米颗粒暴露后神经元分化诱导减少。