کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5550455 1557291 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dual-functional nanoparticles for precise drug delivery to Alzheimer's disease lesions: Targeting mechanisms, pharmacodynamics and safety
ترجمه فارسی عنوان
نانوذرات دوطرفه برای تحویل دقیق دارو به ضایعات بیماری آلزایمر: مکانیزم های هدفمند سازی، دارودودینامیک و ایمنی
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
چکیده انگلیسی

Alzheimer's disease (AD) is the most common form of dementia and is characterized by the cerebral accumulation of extracellular amyloid plaques. In a previous study, this histopathological hallmark was used as a target on a dual-functional nanoparticle (TQNP) to deliver biotechnological drugs, such as the H102 peptide, a β-sheet breaker, to AD lesions precisely. This delivery system could reduce the amyloid-β (Aβ) burden in the brains of AD model mice, as well as ameliorated the memory impairment of the mice. Regretfully, the mechanism how nanoparticles penetrated the BBB and subsequently targeted to the plaques is still unclear. In this study, the internalization, subcellular fate and transportation of the nanoparticles on bEnd.3 cells and an in vitro BBB model, demonstrated that TQNP could be taken up through various routes, including caveolae-mediated endocytosis, suggesting that some of TQNP were able to cross the BBB intact. Then, the TQNP were visualized to specifically bind to the Aβ plaques. TQNP targeting to amyloid plaques might lead to enhanced therapeutic efficacy, which was further evaluated in APP/PS1 transgenic mice. The TQNP/H102 obtained better ability in decreasing amyloid plaques, increasing Aβ-degrading enzymes, reducing tau protein phosphorylation, protecting synapses and improving the spatial learning and memory of transgenic mice than nanoparticles modified with a single ligand. And good biocompatibility of TQNP was indicated with subacute toxicity assays. In conclusion, TQNP was a valuable nanodevice for the precise delivery for biotechnological drugs to treat AD.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 525, Issue 1, 15 June 2017, Pages 237-248
نویسندگان
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