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Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: Structure–function relationships for nanoscale amphiphilic polymers

Paper ID Volume ID Publish Year Pages File Format Full-Text
2271 107 2010 11 PDF Available
Title
Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: Structure–function relationships for nanoscale amphiphilic polymers
Abstract

A family of anionic nanoscale polymers based on amphiphilic macromolecules (AMs) was developed for controlled inhibition of highly oxidized low-density lipoprotein (hoxLDL) uptake by inflammatory macrophage cells, a process that triggers the escalation of a chronic arterial disease called atherosclerosis. The basic AM structure is composed of a hydrophobic portion formed from a mucic acid sugar backbone modified at the four hydroxyls with lauroyl groups conjugated to hydrophilic poly(ethylene glycol) (PEG). The AM structure–activity relationships were probed by synthesizing AMs with six key variables: length of the PEG chain, carboxylic acid location, type of anionic charge, number of anionic charges, rotational motion of the anionic group, and PEG architecture. All AM structures were confirmed by nuclear magnetic resonance spectroscopy and their ability to inhibit hoxLDL uptake in THP-1 human macrophage cells was compared in the absence and presence of serum. We report that AMs with one, rotationally restricted carboxylic acid within the hydrophobic portion of the polymer was sufficient to yield the most effective AM for inhibiting hoxLDL internalization by THP-1 human macrophage cells under serum-containing conditions. Further, increasing the number of charges and altering the PEG architecture in an effort to increase serum stabilization did not significantly impair the ability of AMs to inhibit hoxLDL internalization, suggesting that selected modifications to the AMs could potentially promote multifunctional characteristics of these nanoscale macromolecules.

Keywords
Biomaterials; Polymers; Nanoassemblies; Low-density lipoproteins; Macrophages
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Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: Structure–function relationships for nanoscale amphiphilic polymers
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 6, Issue 8, August 2010, Pages 3081–3091
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