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Genetically engineered exosomes display RVG peptide and selectively enrich a neprilysin variant: a potential formulation for the treatment of Alzheimer's disease.

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机构: [1]The Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Luzhou, China. [2]Department of Cardiology, Shaanxi Institute for Pediatric Diseases, Xi'an Key Laboratory of Children's Health and Diseases, Xi'an Children's Hospital, Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, China. [3]Department of Cardiovascular Medicine, The 1st Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.
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摘要:
Exosome is a promising next generation nano-based drug delivery vehicle. However, the unknown molecular mechanisms underlying its natural tissue tropism and the relatively low quantity of naturally enriched molecules of therapeutic value hamper exosome's clinical application. The aim of the research was to create a targeted and highly efficacious exosome formulation for the treatment of Alzheimer's disease (AD). Genetic engineering techniques combined with co-transfection of parental cells were employed to create an exosome formulation that displays RVG peptide on its surface targeting α7-nAChR and simultaneously enriches a neprilysin variant with increased specificity and efficacy in degrading β amyloid peptide (Aβ). The exosome formulation was preferentially internalised into cell lines in an α7-nAChR expression level-dependent manner. When incubated with Aβ-producing N2a cells, it significantly decreased intracellular and secreted Aβ40 levels, a potency that is superior to exosomes derived from adipose-derived stem cell. When systemically administered into mice, the exosome formulation was preferentially targeted to the hippocampus region of the brain and significantly decreased the expression of proinflammatory genes, IL1α, TNFα and NF-κB, and simultaneously increased the expression of anti-inflammatory gene, IL10. Our exosome formulation may be explored as an over-the-counter treatment for AD.

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出版当年[2021]版:
大类 | 3 区 医学
小类 | 3 区 药学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 药学
第一作者:
第一作者机构: [1]The Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Luzhou, China.
通讯作者:
通讯机构: [1]The Key Laboratory of Medical Electrophysiology of Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Luzhou, China. [2]Department of Cardiology, Shaanxi Institute for Pediatric Diseases, Xi'an Key Laboratory of Children's Health and Diseases, Xi'an Children's Hospital, Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, China. [3]Department of Cardiovascular Medicine, The 1st Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.
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