title: Nanoscale anionic macromolecules for selective retention of low-density lipoproteins.
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.
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers University, 98 Brett Road, C230 Engineering, Piscataway, NJ 08854, USA.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Chnari
authors.forename: Hamed B
authors.initials: HB
authors.lastname: Lari
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Uhrich
authors.forename: Prabhas V
authors.initials: PV
authors.lastname: Moghe
mesh_terms: D000838:Anions; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy; D040761:Biomimetic Materials; D001781:Blood Component Removal / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006025:Glycosaminoglycans / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry* / Q000627:therapeutic use*; D008823:Micelles; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D000838:Anions; D004337:Drug Carriers; D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D046911:Macromolecular Substances; D008823:Micelles