Nanoscale anionic macromolecules for selective retention of low-density lipoproteins

Evangelia Chnari, Hamed B. Lari, Lu Tian, Kathryn E. Uhrich, Prabhas V. Moghe

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Synthetically designed anionic nanocarriers that mimic the charge properties of glycosaminoglycans can potentially sequester low-density lipoproteins (LDL) during the treatment of atherosclerosis. In this study, we explore the LDL retentivity of 15-20 nm anionic micelles formed from amphiphilic scorpion-like macromolecules (AScMs) as building blocks. The macromolecules comprise four aliphatic chains attached to mucic acid and a linear polyethylene glycol (PEG) segment to form micellar nanocarriers with a hydrophobic core and hydrophilic corona. Dynamic light scattering and transmission electron microscopy studies indicate that the carboxylate-terminated nanocarriers (20 nm) sequester LDL (22 nm), resulting in complexes with a diameter of 60-90 nm, but neutral ethoxy-terminated nanocarriers do not retain LDL. Further, carboxylate-terminated nanocarriers consistently bound to unoxidized LDL (Relative Electrophoretic Mobility, REM=1.0) and mildly oxidized LDL (REM=1.5), but not highly oxidized LDL (REM=3.6), whereas the neutral nanocarriers displayed no preference/affinity at all, indicating that the nanocarrier-LDL binding is charge-dependent. The binding affinity of unoxidized LDL for differentially charged nanocarriers, formed from varying ratios of carboxylate- and ethoxy-terminated macromolecules, was quantified. The 100% carboxylated nanocarriers elicited the highest binding affinity (K d=567 nm), whereas mixed micelles elicited significantly lower levels of binding affinity. Our results highlight the promise of synthetically designed nanomaterials in lipoprotein retention, a key step in managing the escalation of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)3749-3758
Number of pages10
JournalBiomaterials
Volume26
Issue number17
DOIs
StatePublished - Jun 2005

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Keywords

  • Amphiphilic macromolecules
  • Atherosclerosis
  • Low-density lipoproteins
  • Micelles
  • Nanotechnology

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