Amphiphilic nanoparticles repress macrophage atherogenesis: Novel core/shell designs for scavenger receptor targeting and down-regulation

Latrisha K. Petersen, Adam W. York, Daniel R. Lewis, Sonali Ahuja, Kathryn E. Uhrich, Robert K. Prudhomme, Prabhas V. Moghe

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Atherosclerosis, an inflammatory lipid-rich plaque disease is perpetuated by the unregulated scavenger-receptor-mediated uptake of oxidized lipoproteins (oxLDL) in macrophages. Current treatments lack the ability to directly inhibit oxLDL accumulation and foam cell conversion within diseased arteries. In this work, we harness nanotechnology to design and fabricate a new class of nanoparticles (NPs) based on hydrophobic mucic acid cores and amphiphilic shells with the ability to inhibit the uncontrolled uptake of modified lipids in human macrophages. Our results indicate that tailored NP core and shell formulations repress oxLDL internalization via dual complementary mechanisms. Specifically, the most atheroprotective molecules in the NP cores competitively reduced NP-mediated uptake to scavenger receptor A (SRA) and also down-regulated the surface expression of SRA and CD36. Thus, nanoparticles can be designed to switch activated, lipid-scavenging macrophages to antiatherogenic phenotypes, which could be the basis for future antiatherosclerotic therapeutics.

Original languageEnglish (US)
Pages (from-to)2815-2824
Number of pages10
JournalMolecular Pharmaceutics
Volume11
Issue number8
DOIs
StatePublished - Aug 4 2014

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Keywords

  • amphiphilic macromolecules
  • atherogenesis
  • atherosclerosis
  • macrophages
  • nanoparticle
  • oxidized lipoproteins
  • scavenger receptor

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