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Dual-functional nanoparticles targeting amyloid plaques in the brains of Alzheimer's disease mice

Paper ID Volume ID Publish Year Pages File Format Full-Text
6236 468 2014 10 PDF Available
Title
Dual-functional nanoparticles targeting amyloid plaques in the brains of Alzheimer's disease mice
Abstract

Alzheimer's disease (AD) is a common neurodegenerative disorder with few treatments. The limitations imposed by the blood–brain barrier (BBB) and the non-selective distribution of drugs in the brain have hindered the effective treatment of AD and may result in severe side effects on the normal brains. We developed a dual-functional nanoparticle drug delivery system based on a PEGylated poly (lactic acid) (PLA) polymer. Two targeting peptides that were screened by phage display, TGN and QSH, were conjugated to the surface of the nanoparticles. TGN specifically targets ligands at the BBB, while QSH has good affinity with Aβ1-42, which is the main component of amyloid plaque. Tests probing the bEnd.3 cell uptake and in vivo imaging were conducted to determine the best density of TGN on the nanoparticles' surfaces. The optimal amount of QSH was studied using a Thioflavin T (ThT) binding assay and surface plasmon resonance (SPR) experiments. The optimal maleimide/peptide molar ratio was 3 for both TGN and QSH on the surface of the nanoparticles (T3Q3-NP), and these nanoparticles achieved enhanced and precise targeted delivery to amyloid plaque in the brains of AD model mice. A MTT assay also validated the safety of this dual-targeted delivery system; little cytotoxicity was demonstrated with both bEnd.3 and PC 12 cells. In conclusion, the T3Q3-NP might be a valuable targeting system for AD diagnosis and therapy.

Keywords
Dual-functional nanoparticles; Blood–brain barrier (BBB); Aβ1-42 peptide; Alzheimer's disease (AD)
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Dual-functional nanoparticles targeting amyloid plaques in the brains of Alzheimer's disease mice
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 1, January 2014, Pages 456–465
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us