Sustained release of bioactive hydrogen by Pd hydride nanoparticles overcomes Alzheimer's disease. (March 2019)

• Record Type: Journal Article
• Authors: Zhang, Lei; Zhao, Penghe; Yue, Caiping; Jin, Zhaokui; Liu, Qiong; Du, Xiubo; He, Qianjun
• Is Part Of: Biomaterials. Volume 197(2019)
• Page Start: 393
• Page End: 404
• Publication Date: 2019-03
• Subjects: Alzheimer's disease -- Controlled release -- Drug delivery -- Hydrogen therapy -- Nanoparticles; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2019.01.037
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: 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 and in situ sustained 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 A β generation 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.