title: Amphiphilic nanoparticles repress macrophage atherogenesis: novel core/shell designs for scavenger receptor targeting and down-regulation.
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.
authors: Department of Biomedical Engineering, Rutgers University , 599 Taylor Road, Piscataway, New Jersey 08854, United States.
authors: Latrisha K
authors: LK
authors: Petersen
authors: Adam W
authors: AW
authors: York
authors: Daniel R
authors: DR
authors: Lewis
authors: Sonali
authors: S
authors: Ahuja
authors: Kathryn E
authors: KE
authors: Uhrich
authors: Robert K
authors: RK
authors: Prud'homme
authors: Prabhas V
authors: PV
authors: Moghe
mesh_terms: D001161:Arteriosclerosis / Q000378:metabolism; D050197:Atherosclerosis; D018955:CD36 Antigens / Q000737:chemistry; D015536:Down-Regulation; D005487:Foam Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear; D050356:Lipid Metabolism / Q000235:genetics; D008074:Lipoproteins / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D051117:Scavenger Receptors, Class A / Q000737:chemistry*
chemical_list: D018955:CD36 Antigens; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D051117:Scavenger Receptors, Class A; C099252:oxidized low density lipoprotein