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- W3048402510 endingPage "725" @default.
- W3048402510 startingPage "714" @default.
- W3048402510 abstract "Targeting gene-based therapeutics to the brain is a strategy actively sought to treat Alzheimer's disease (AD). Recent findings discovered the role of apolipoprotein E (ApoE) isoforms in the clearance of toxic amyloid beta proteins from the brain. ApoE2 isoform is beneficial for preventing AD development, whereas ApoE4 is a major contributing factor to the disease. In this paper, we demonstrated efficient brain-targeted delivery of ApoE2 encoding plasmid DNA (pApoE2) using glucose transporter-1 (glut-1) targeted liposomes. Liposomes were surface-functionalized with a glut-1 targeting ligand mannose (MAN) and a cell-penetrating peptide (CPP) to enhance brain-targeting and cellular internalization, respectively. Among various CPPs, rabies virus glycoprotein peptide (RVG) or penetratin (Pen) was selected as a cell-penetration enhancer. Dual (RVGMAN and PenMAN)-functionalized liposomes were cytocompatible at 100 nM phospholipid concentration and demonstrated significantly higher expression of ApoE2 in bEnd.3 cells, primary neurons, and astrocytes compared to monofunctionalized and unmodified (plain) liposomes. Dual-modified liposomes also showed ∼2 times higher protein expression than other formulation controls in neurons cultured below the in vitro BBB model. These results translated well to in vivo efficacy study with significantly higher transfection of pApoE2 in the C57BL/6 mice brain following single tail vein administration of RVGMAN and PenMAN functionalized liposomes without any noticeable signs of toxicity. These results illustrate the potential of surface-modified liposomes for safe and brain-targeted delivery of the pApoE2 gene for effective AD therapy." @default.
- W3048402510 created "2020-08-18" @default.
- W3048402510 creator A5003571906 @default.
- W3048402510 creator A5035758532 @default.
- W3048402510 creator A5041734187 @default.
- W3048402510 date "2020-08-11" @default.
- W3048402510 modified "2023-10-12" @default.
- W3048402510 title "Design and Validation of Liposomal ApoE2 Gene Delivery System to Evade Blood–Brain Barrier for Effective Treatment of Alzheimer’s Disease" @default.
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- W3048402510 doi "https://doi.org/10.1021/acs.molpharmaceut.0c00461" @default.
- W3048402510 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32787268" @default.
- W3048402510 hasPublicationYear "2020" @default.
- W3048402510 type Work @default.