Controllable inhibition of cellular uptake of oxidized low-density lipoprotein

Structure-function relationships for nanoscale amphiphilic polymers

Nicole M Iverson, Sarah M. Sparks, Bahar Demirdirek, Kathryn E. Uhrich, Prabhas V. Moghe

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3081-3091
Number of pages11
JournalActa Biomaterialia
Volume6
Issue number8
DOIs
StatePublished - Jan 1 2010

Fingerprint

Lipoproteins
Macromolecules
Polymers
Macrophages
Carboxylic Acids
Polyethylene glycols
Serum
Ethylene Glycol
Structure-Activity Relationship
Hydroxyl Radical
Atherosclerosis
Chronic Disease
Magnetic Resonance Spectroscopy
Carboxylic acids
oxidized low density lipoprotein
Sugars
Nuclear magnetic resonance spectroscopy
Stabilization

Keywords

  • Biomaterials
  • Low-density lipoproteins
  • Macrophages
  • Nanoassemblies
  • Polymers

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

Controllable inhibition of cellular uptake of oxidized low-density lipoprotein : Structure-function relationships for nanoscale amphiphilic polymers. / Iverson, Nicole M; Sparks, Sarah M.; Demirdirek, Bahar; Uhrich, Kathryn E.; Moghe, Prabhas V.

In: Acta Biomaterialia, Vol. 6, No. 8, 01.01.2010, p. 3081-3091.

Research output: Contribution to journalArticle

Iverson, Nicole M ; Sparks, Sarah M. ; Demirdirek, Bahar ; Uhrich, Kathryn E. ; Moghe, Prabhas V. / Controllable inhibition of cellular uptake of oxidized low-density lipoprotein : Structure-function relationships for nanoscale amphiphilic polymers. In: Acta Biomaterialia. 2010 ; Vol. 6, No. 8. pp. 3081-3091.
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