Multifunctional Selenium Quantum Dots for the Treatment of Alzheimer’s Disease by Reducing Aβ-Neurotoxicity and Oxidative Stress and Alleviate Neuroinflammation

神经炎症 氧化应激 材料科学 神经毒性 体内 血脑屏障 疾病 医学 药理学 神经科学 化学 生物 中枢神经系统 生物化学 毒性 病理 内科学 生物技术
作者
Xian Guo,Qiaoshan Lie,Yanan Liu,Jia Zhi,Youcong Gong,Xiaoyu Yuan,Jie Liu
出处
期刊:ACS Applied Materials & Interfaces [American Chemical Society]
卷期号:13 (26): 30261-30273 被引量:89
标识
DOI:10.1021/acsami.1c00690
摘要

At present, the complex pathogenesis, the difficult-to-overcome blood-brain barrier (BBB), the development of the disease course which cannot be prevented, and other problems are serious challenges in the treatment of Alzheimer's disease (AD). In order to enhance the therapeutic effect of drugs through BBB, we synthesized simple and easy-to-obtain selenium quantum dots (SeQDs), with a multitarget therapeutic effect. This new type of SeQDs has an ultrasmall size and can quickly penetrate the BBB. According to the fluorescence characteristics of SeQDs, we can diagnose and track AD. The experimental results show that SeQDs have strong free-radical scavenging activity, protect cells from oxidative stress induced by different stimuli, and show broad-spectrum antioxidant activity. The SeQDs can not only effectively inhibit Aβ aggregation and significantly reduce Aβ-mediated cytotoxicity, thus preventing AD cascade reaction, but also effectively reduce tau protein phosphorylation by down-regulating PHF1 and CP13 and further reduce oxidative stress, restore mitochondrial functions, and maintain nerve cell stability and protect nerve cells from oxidative stress. In vivo studies demonstrate that SeQDs can continuously accumulate in the brain after rapid passage of BBB and can quickly alleviate AD, significantly improve the memory impairment of AD mice, and improve their learning and memory ability. Therefore, the use of SeQDs in the treatment of AD has great advantages compared with traditional single-target drugs and provides a new direction for the combination of prevention and treatment of neurodegenerative diseases.
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