Sustained release of bioactive hydrogen by Pd hydride nanoparticles overcomes Alzheimer's disease
Sustained release of bioactive hydrogen by Pd hydride nanoparticles overcomes Alzheimer's disease
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氢化钯纳米颗粒持续释放生物活性氢可克服阿尔茨海默病
DOI：
10.1016/j.biomaterials.2019.01.037
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发表时间：
2019
期刊：
影响因子：
14
通讯作者：
Qianjun He
中科院分区：
文献类型：
--
作者：
Lei Zhang;Penghe Zhao;Caiping Yue;Zhaokui Jin;Qiong Liu;Xiubo Du;Qianjun He
氧化应激诱导的线粒体功能障碍在阿尔茨海默病（AD）的发病机制中起重要作用。氢分子是一种特殊的抗氧化剂，可以选择性地清除高细胞毒性的活性氧，如·OH，显示出通过减少氧化应激治疗AD的潜力。然而，由于给药氢在AD脑内的溶解度较低，没有有效的途径实现氢在AD脑内的持续高效积累。在这里，我们开发了小尺寸的氢化Pd （PdH）纳米颗粒，用于高氢载荷和在AD大脑中持续释放氢。由于Pd的催化加氢作用，PdH纳米颗粒释放的氢具有较高的生物还原性，有利于以自催化的方式有效清除细胞毒性·OH。生物还原氢能够通过消除氧化应激，激活抗氧化通路，恢复线粒体功能障碍，抑制a β的生成和聚集，阻断突触和神经元凋亡，促进神经元能量代谢，从而改善AD小鼠的认知功能障碍。提出的氢释放纳米药物策略将为阿尔茨海默病的治疗打开一扇新的窗口。
Oxidative stress-induced mitochondrial dysfunction plays an important role in the pathogenesis of Alzheimer's disease (AD). Hydrogen molecule, a special antioxidant, can selectively scavenge highly cytotoxic reactive oxygen species such as ·OH, exhibiting a potential to treat AD by reducing oxidative stress. However, there is no effective route to realize the continuous and efficient accumulation of administrated hydrogen in AD brain owing to its low solubility. Here, we develop the small-sized Pd hydride (PdH) nanoparticles for high payload of hydrogen andin situsustained hydrogen release in AD brain. By virtue of the catalytic hydrogenation effect of Pd, the released hydrogen from PdH nanoparticles exhibits high bio-reductivity in favor of effectively scavenging cytotoxic ·OH in a self-catalysis way. Bio-reductive hydrogen is able to recover mitochondrial dysfunction, inhibit Aβgeneration and aggregation, block synaptic and neuronal apoptosis and promote neuronal energy metabolism by eliminating oxidative stress and activating the anti-oxidative pathway, consequently ameliorating the cognitive impairment in AD mice. The proposed hydrogen-releasing nanomedicine strategy would open a new window for the treatment of AD.