Document Detail


Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: structure-function relationships for nanoscale amphiphilic polymers.
MedLine Citation:
PMID:  20170758     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Nicole M Iverson; Sarah M Sparks; Bahar Demirdirek; Kathryn E Uhrich; Prabhas V Moghe
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-17
Journal Detail:
Title:  Acta biomaterialia     Volume:  6     ISSN:  1878-7568     ISO Abbreviation:  Acta Biomater     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-06-09     Completed Date:  2010-09-13     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  101233144     Medline TA:  Acta Biomater     Country:  England    
Other Details:
Languages:  eng     Pagination:  3081-91     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Anions
Carboxylic Acids / chemistry
Cell Line
Endocytosis / drug effects*
Humans
Hydrophobic and Hydrophilic Interactions
Lipoproteins, LDL / metabolism*
Macrophages / drug effects,  metabolism*
Nanostructures / chemistry*
Particle Size*
Polyethylene Glycols / chemical synthesis,  chemistry
Polymers / chemistry*,  pharmacology*
Rotation
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
HL 093753/HL/NHLBI NIH HHS; R01 HL107913/HL/NHLBI NIH HHS; R21 HL093753/HL/NHLBI NIH HHS; R21 HL093753-01A2/HL/NHLBI NIH HHS; R21 HL093753-01A2S1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anions; 0/Carboxylic Acids; 0/Lipoproteins, LDL; 0/Polyethylene Glycols; 0/Polymers; 0/oxidized low density lipoprotein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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