Tsai Yuan-Chung, Luo Jing-Chian, Liu Te-I, Lu I-Lin, Shen Ming-Yin, Chuang Chun-Yu, Chern Chorng-Shyan, Chiu Hsin-Cheng
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of Surgery, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan.
Nanomaterials (Basel). 2020 Jun 30;10(7):1284. doi: 10.3390/nano10071284.
Soluble amyloid-β oligomers (oAβ)-induced neuronal death and inflammation response has been recognized as one of the major causes of Alzheimer's disease (AD). In this work, a novel strategy adopting silica-coated iron oxide stir bar (MSB)-based AD therapy system via magnetic stirring-induced capture of oAβ into magnetic plaques (mpAβ) and activation of microglia on cellular plaque clearance was developed. With oAβ being effectively converted into mpAβ, the neurotoxicity toward neuronal cells was thus greatly reduced. In addition to the good preservation of neurite outgrowth through the diminished uptake of oAβ, neurons treated with oAβ under magnetic stirring also exhibited comparable neuron-specific protein expression to those in the absence of oAβ. The phagocytic uptake of mpAβ by microglia was enhanced significantly as compared to the counterpart of oAβ, and the M1 polarization of microglia often occurring after the uptake of oAβ restricted to an appreciable extent. As a result, the inflammation induced by pro-inflammatory cytokines was greatly alleviated.
可溶性淀粉样β寡聚体（oAβ）诱导的神经元死亡和炎症反应已被认为是阿尔茨海默病（AD）的主要病因之一。在这项工作中，开发了一种基于二氧化硅包覆的氧化铁搅拌棒（MSB）的新型AD治疗系统策略，通过磁搅拌将oAβ捕获到磁性斑块（mpAβ）中，并激活小胶质细胞进行细胞斑块清除。随着oAβ有效地转化为mpAβ，对神经元细胞的神经毒性因此大大降低。除了通过减少oAβ的摄取来良好地保留神经突生长外，在磁搅拌下用oAβ处理的神经元还表现出与不存在oAβ时相当的神经元特异性蛋白表达。与oAβ相比，小胶质细胞对mpAβ的吞噬摄取显著增强，并且oAβ摄取后经常发生的小胶质细胞M1极化受到明显限制。结果，促炎细胞因子诱导的炎症得到了极大缓解。
