Journal
BIOMATERIALS
Volume 197, Issue -, Pages 417-431Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.12.027
Keywords
Alzheimer's disease; Progressive release; H2O2 response; Synergistic therapy
Funding
- National Natural Science Foundation of China [21877051, 81803027, 21371075]
- Natural Science Foundation of Guangdong Province [2014A030311025]
- Planned Item of Science and Technology of Guangdong Province [2016A020217011]
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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-beta-CD/Bor) based on the borneol (Bor) target, beta-cyclodextrin nanovalves (Fc-beta-CD) with loaded resveratrol (Res). Previous experiments have shown that MSe-Res/Fc-beta-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-beta-CD is opened by the redox (H2O2) response to the release of Res at the lesion site. We demonstrated that MSe-Res/Fc-beta-CD/Bor inhibited aggregation of beta-amyloid proteins (A beta), 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-beta-CD/Bor loaded with Riv had a better pharmacokinetic index. These results indicate that MSe-Res/Fc-beta-CD/Bor could be a prospective drug for treating AD.
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