Brain-targeted co-delivery of β-amyloid converting enzyme 1 shRNA and epigallocatechin-3-gallate by multifunctional nanocarriers for Alzheimer's disease treatment.

IUBMB Life
Lijie LvJiuli Yuan

Abstract

Progressive memory loss and cognitive dysfunction are hallmark clinical features of Alzheimer's disease (AD). As a possible treatment for AD, we developed an epigallocatechin-3-gallate (EGCG) and β-site amyloid precursor protein (APP) cleaving enzyme 1 antisense (BACE1-AS) shRNA-encoded plasmid. The plasmid was loaded on to RVG29 peptide-targeted multifunctional nanoparticles (NPs) (REGS-PN). The polymeric NPs were characterized by flow cytometry, biocompatibility assay, pharmacokinetic analysis, Western blot analysis, and the Morris water maze (MWM) test. The differences in plasma and brain NP accumulation following intravenous administration showed a significantly longer circulation time for EGS-PN and REGS-PN in the blood stream. In contrast, free EGCG was rapidly eliminated from the circulation. REGS-PM successfully travelled through the blood-brain barrier and was present at a higher concentration in the brain compared with both non-targeted NPs and free EGCG. REGS-PN administration to APPswe/PS1dE9 double transgenic mice (APP/PS1 mice) resulted in downregulation of the key enzyme in amyloid-β formation (BACE1) and amyloid beta, indicating synergistic therapeutic activity. The MWM test revealed that simultaneous delivery o...Continue Reading

References

Mar 17, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Moses O OyewumiRussell J Mumper
Jan 12, 2005·The Journal of Cell Biology·Edward B LeeVirginia M-Y Lee
Dec 16, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Fiona M LairdPhilip C Wong
Dec 20, 2005·Lancet·Cleusa P FerriUNKNOWN Alzheimer's Disease International
May 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·Huifang MaKaren H Ashe
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ying JiangRalph A Nixon
Sep 15, 2014·Protein Expression and Purification·Yu-Jiao YangXian-Zhu Xia
Mar 31, 2015·Annals of Clinical and Translational Neurology·Jeffrey L CummingsDrew M Velting
Dec 9, 2015·European Journal of Pharmacology·James Cheng-Chung WeiChih-Li Lin
Feb 24, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Animesh ChowdhurySajal Chakraborti
May 5, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Thiruganesh RamasamyJong Oh Kim
Jul 16, 2019·The Journal of Pharmacy and Pharmacology·Seetha HarilalBijo Mathew
Apr 22, 2020·Brain Research Bulletin·Seetha HarilalBijo Mathew

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