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Multifunctional Selenium Quantum Dots for the Treatment of Alzheimer’s Disease by Reducing Aβ-Neurotoxicity and Oxidative Stress and Alleviate Neuroinflammation
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-06-25 , DOI: 10.1021/acsami.1c00690 Xian Guo 1 , Qiaoshan Lie 1 , Yanan Liu 1, 2 , Zhi Jia 1 , Youcong Gong 1 , Xiaoyu Yuan 1 , Jie Liu 1
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-06-25 , DOI: 10.1021/acsami.1c00690 Xian Guo 1 , Qiaoshan Lie 1 , Yanan Liu 1, 2 , Zhi Jia 1 , Youcong Gong 1 , Xiaoyu Yuan 1 , Jie Liu 1
Affiliation
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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.
中文翻译：
多功能硒量子点通过降低 Aβ-神经毒性和氧化应激和缓解神经炎症来治疗阿尔茨海默病
目前，复杂的发病机制、难以克服的血脑屏障（BBB）、无法预防的病程发展等问题是阿尔茨海默病（AD）治疗面临的严峻挑战。为了通过血脑屏障增强药物的治疗效果，我们合成了简单易得的硒量子点（SeQDs），具有多靶点治疗作用。这种新型 SeQD 具有超小尺寸，可以快速穿透 BBB。根据SeQDs的荧光特性，我们可以诊断和追踪AD。实验结果表明，SeQDs具有很强的自由基清除活性，保护细胞免受不同刺激引起的氧化应激，并表现出广谱的抗氧化活性。SeQDs不仅可以有效抑制Aβ聚集，显着降低Aβ介导的细胞毒性，从而防止AD级联反应，还可以通过下调PHF1和CP13有效降低tau蛋白磷酸化，进一步降低氧化应激，恢复线粒体功能，维持神经细胞稳定性和保护神经细胞免受氧化应激。体内研究表明，SeQDs在BBB快速通过后可在脑内持续积累，能迅速缓解AD，显着改善AD小鼠的记忆障碍，提高其学习记忆能力。因此，使用SeQDs治疗AD与传统的单靶点药物相比具有很大的优势，为神经退行性疾病的防治结合提供了新的方向。
更新日期：2021-07-07
中文翻译：
多功能硒量子点通过降低 Aβ-神经毒性和氧化应激和缓解神经炎症来治疗阿尔茨海默病
目前，复杂的发病机制、难以克服的血脑屏障（BBB）、无法预防的病程发展等问题是阿尔茨海默病（AD）治疗面临的严峻挑战。为了通过血脑屏障增强药物的治疗效果，我们合成了简单易得的硒量子点（SeQDs），具有多靶点治疗作用。这种新型 SeQD 具有超小尺寸，可以快速穿透 BBB。根据SeQDs的荧光特性，我们可以诊断和追踪AD。实验结果表明，SeQDs具有很强的自由基清除活性，保护细胞免受不同刺激引起的氧化应激，并表现出广谱的抗氧化活性。SeQDs不仅可以有效抑制Aβ聚集，显着降低Aβ介导的细胞毒性，从而防止AD级联反应，还可以通过下调PHF1和CP13有效降低tau蛋白磷酸化，进一步降低氧化应激，恢复线粒体功能，维持神经细胞稳定性和保护神经细胞免受氧化应激。体内研究表明，SeQDs在BBB快速通过后可在脑内持续积累，能迅速缓解AD，显着改善AD小鼠的记忆障碍，提高其学习记忆能力。因此，使用SeQDs治疗AD与传统的单靶点药物相比具有很大的优势，为神经退行性疾病的防治结合提供了新的方向。
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