Bioactive superparamagnetic iron oxide-gold nanoparticles regulated by a dynamic magnetic field induce neuronal Ca2+ influx and differentiation
Bioactive superparamagnetic iron oxide-gold nanoparticles regulated by a dynamic magnetic field induce neuronal Ca2+ influx and differentiation
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DOI：
10.1016/j.bioactmat.2023.01.007
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发表时间：
2023-08-01
影响因子：
18.9
通讯作者：
Qin, Yi-Xian
中科院分区：
文献类型：
--
作者：
Georgas, Elias;Yuan, Muzhaozi;Qin, Yi-Xian
治疗神经变性疾病，例如，阿尔茨海默氏病由于大脑中有限的神经再生率而仍然是一个重大挑战。本研究的目的是评估以下假设：神经生长因子功能化的超顺磁性氧化铁-金（NGFSPIO-Au）纳米颗粒（NPs）的外部磁场（MF）刺激可以诱导Ca 2+内流、膜去极化和增强神经元分化，其中动态MF（DMF）优于静态MF（SMF）调节。结果显示，与DMF单独刺激和SMF + NGF-SPIO-Au NPs刺激相比，DMF（1 Hz，0.5 T，30 min）+NGF-SPIO-Au NPs刺激PC-12细胞后，细胞内总Ca 2+内流分别增加了300%和535%，这归因于连续的膜去极化。应用叠氮化钠进行的细胞摄取证明DMF通过内吞作用增强NGF-SPIO-Au NP的细胞摄取。此外，DMF上调神经分化标志物（β 3-微管蛋白）和细胞粘附分子（整合素-β 1）与NGF-SPIO-Au NPs的存在，而SMF没有显示这些效果。结果表明，非侵入性DMF刺激的NPs可以调节细胞内Ca 2+内流，增强神经元分化和神经再生速率。
Treating neurodegenerative diseases, e.g., Alzheimer's Disease, remains a significant challenge due to the limited neuroregeneration rate in the brain. The objective of this study is to evaluate the hypothesis that external magnetic field (MF) stimulation of nerve growth factor functionalized superparamagnetic iron oxide-gold (NGFSPIO-Au) nanoparticles (NPs) can induce Ca2+ influx, membrane depolarization, and enhance neuron differentiation with dynamic MF (DMF) outperforming static MF (SMF) regulation. We showed the that total intracellular Ca2+ influx of PC-12 cells was improved by 300% and 535% by the stimulation of DMF (1 Hz, 0.5 T, 30min) with NGF-SPIO-Au NPs compared to DMF alone and SMF with NGF-SPIO-Au NPs, respectively, which was attributed to successive membrane depolarization. Cellular uptake performed with the application of sodium azide proved that DMF enhanced cellular uptake of NGF-SPIO-Au NPs via endocytosis. In addition, DMF upregulated both the neural differentiation marker (beta 3-tubulin) and the cell adhesive molecule (integrin-beta 1) with the existence of NGF-SPIO-Au NPs, while SMF did not show these effects. The results imply that noninvasive DMF-stimulated NPs can regulate intracellular Ca2+ influx and enhance neuron differentiation and neuroregeneration rate.