Progressive release of mesoporous nano-selenium delivery system for the multi-channel synergistic treatment of Alzheimer's disease
Progressive release of mesoporous nano-selenium delivery system for the multi-channel synergistic treatment of Alzheimer's disease
复制标题
渐进式释放介孔纳米硒输送系统用于多通道协同治疗阿尔茨海默病
DOI：
10.1016/j.biomaterials.2018.12.027
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发表时间：
2019
期刊：
影响因子：
14
通讯作者：
Liu Jie
中科院分区：
文献类型：
--
作者：
Sun Jing;Wei Chunfang;Liu Yanan;Xie Wenjie;Xu Mengmeng;Zhou Hui;Liu Jie
阿尔茨海默病(AD)是一种发病机制复杂的神经退行性疾病。控释、靶向能力和多渠道协同治疗是AD药物成功的关键因素。在这里，我们报道了一种基于冰片(BOR)靶标的新型介孔纳米硒释放系统(MSE-RES/FC-β-CD/BOR)，即负载白藜芦醇(RES)的β-环糊精纳米瓣膜(FC-β-CD)。先前的实验表明，MSE-RES/FC-β-CD/BOR首先通过与血液或细胞内酯酶相互作用释放BOR，使纳米系统通过血脑屏障。随后，Fc-β-CD通过病变部位RES的释放而被氧化还原(H2O2)反应打开。我们证明，MSe-RES/FC-β-CD/Bor可抑制β-淀粉样蛋白(Aβ)的聚集，减轻氧化应激，抑制tau过度磷酸化，同时保护神经细胞并成功改善APP/PS1小鼠的记忆障碍。有趣的是，与单用利凡斯明(RIV)阳性药物相比，负载RIV的MSE/FC-β-CD/BOR具有更好的药代动力学指标。这些结果表明MSE-RES/FC-β-CD/BOR可能是一种治疗AD的潜在药物。
Alzheimer's disease (AD) is a neurodegenerative disease with a complex pathogenesis. Controlled release, target ability, and multi-channel synergistic treatment are key factors associated with the success of AD drugs. Herein, we report a novel mesoporous nano-selenium (MSe) release delivery system (MSe-Res/Fc-β-CD/Bor) based on the borneol (Bor) target, β-cyclodextrin nanovalves (Fc-β-CD) with loaded resveratrol (Res). Previous experiments have shown that MSe-Res/Fc-β-CD/Bor first releases Bor by interacting with blood or intracellular esterases, allowing the nanosystem to pass through the blood-brain barrier (BBB). Subsequently, the Fc-β-CD is opened by the redox (H2O2) response to the release of Res at the lesion site. We demonstrated that MSe-Res/Fc-β-CD/Bor inhibited aggregation of β-amyloid proteins (Aβ), mitigated oxidative stress, and suppressed tau hyperphosphorylation, while protecting nerve cells and successfully improving memory impairment in APP/PS1 mice. Interestingly, compared with rivastigmine (Riv) positive drugs alone, the MSe/Fc-β-CD/Bor loaded with Riv had a better pharmacokinetic index. These results indicate that MSe-Res/Fc-β-CD/Bor could be a prospective drug for treating AD.