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Lipid-based nanoparticles with high binding affinity for amyloid-β1–42 peptide

Paper ID Volume ID Publish Year Pages File Format Full-Text
9153 618 2010 11 PDF Available
Title
Lipid-based nanoparticles with high binding affinity for amyloid-β1–42 peptide
Abstract

The neurotoxic beta-amyloid peptide (Aβ), formed in anomalous amounts in Alzheimer’s disease (AD), is released as monomer and then undergoes aggregation forming oligomers, fibrils and plaques in diseased brains. Aβ aggregates are considered as possible targets for therapy and/or diagnosis of AD. Since nanoparticles (NPs) are promising vehicles for imaging probes and therapeutic agents, we realized and characterized two types of NPs (liposomes and solid lipid nanoparticles, 145 and 76 nm average size, respectively) functionalized to target Aβ1–42 with high affinity. Preliminary immunostaining studies identified anionic phospholipids [phosphatidic acid (PA) and cardiolipin (CL)] as suitable Aβ1–42 ligands. PA/CL-functionalized, but not plain, NPs interacted with Aβ1–42 aggregates as indicated by ultracentrifugation experiments, in which binding reaction occurred in solution, and by Surface Plasmon Resonance (SPR) experiments, in which NPs flowed onto immobilized Aβ1–42. All these experiments were carried out in buffered saline. SPR studies indicated that, when exposed on NPs surface, PA/CL display very high affinity for Aβ1–42 fibrils (22–60 nm), likely because of the occurrence of multivalent interactions which markedly decrease the dissociation of PA/CL NPs from Aβ. Noteworthy, PA/CL NPs did not bind to bovine serum albumin. The PA/CL NPs described in this work are endowed with the highest affinity for Aβ so far reported. These characteristics make our NPs a very promising vector for the targeted delivery of potential new diagnostic and therapeutic molecules to be tested in appropriate animal models.

Keywords
Nanoparticles; Drug delivery; Affinity; Lipid; Liposome; Aβ-peptide
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Lipid-based nanoparticles with high binding affinity for amyloid-β1–42 peptide
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 25, September 2010, Pages 6519–6529
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