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Biomaterials. 2019 Mar;197:393-404. doi: 10.1016/j.biomaterials.2019.01.037. Epub 2019 Jan 24.

Sustained release of bioactive hydrogen by Pd hydride nanoparticles overcomes Alzheimer's disease.

Author information

1
Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, No. 1066 Xueyuan Road, Nanshan District, Shenzhen, 518060, Guangdong, China.
2
Guangdong Provincial Key Laboratory of Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Health Science Center, Shenzhen University, No. 1066 Xueyuan Road, Nanshan District, Shenzhen, 518060, Guangdong, China.
3
Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, No. 1066 Xueyuan Road, Nanshan District, Shenzhen, 518060, Guangdong, China. Electronic address: duxiubo@szu.edu.cn.
4
Guangdong Provincial Key Laboratory of Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Health Science Center, Shenzhen University, No. 1066 Xueyuan Road, Nanshan District, Shenzhen, 518060, Guangdong, China. Electronic address: nanoflower@126.com.

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 Aβ 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.

KEYWORDS:

Alzheimer's disease; Controlled release; Drug delivery; Hydrogen therapy; Nanoparticles

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