Nanoscale amphiphilic macromolecules as lipoprotein inhibitors: The role of charge and architecture

Jinzhong Wang, Nicole M. Plourde, Nicole Iverson, Prabhas V. Moghe, Kathryn E. Uhrich

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

A series of novel amphiphilic macromolecules composed of alkyl chains as the hydrophobic block and poly(ethylene glycol) as the hydrophilic block were designed to inhibit highly oxidized low density lipoprotein (hoxLDL) uptake by synthesizing macromolecules with negatively charged moieties (ie, carboxylic acids) located in the two different blocks. The macromolecules have molecular weights around 5,500 g/mol, form micelles in aqueous solution with an average size of 20-35 nm, and display critical micelle concentration values as low as 10-7 M. Their charge densities and hydrodynamic size in physiological buffer solutions correlated with the hydrophobic/hydrophilic block location and quantity of the carboxylate groups. Generally, carboxylate groups located in the hydrophobic block destabilize micelle formation more than carboxylate groups in the hydrophilic block. Although all amphiphilic macromolecules inhibited unregulated uptake of hoxLDL by macrophages, inhibition efficiency was influenced by the quantity and location of the negatively charged-carboxylate on the macromolecules. Notably, negative charge is not the sole factor in reducing hoxLDL uptake. The combination of smaller size, micellar stability and charge density is critical for inhibiting hoxLDL uptake by macrophages.

Original languageEnglish (US)
Pages (from-to)697-705
Number of pages9
JournalInternational journal of nanomedicine
Volume2
Issue number4
StatePublished - Dec 1 2007

Keywords

  • Amphiphilic macromolecules
  • Highly oxidized low-density lipoproteins
  • Polymeric micelles
  • Scavenger receptor inhibition

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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