Nanoblockers Fight Atherosclerosis

Heart researchers have used nanotechnology to engineer a molecule that blocks the ability of macrophages to ingest oxidized LDL (low density lipoprotein), which prevents the formation of foam cells, key initiators of atherosclerotic plaques.

The "nanoblockers” are macromolecules containing mucic acid, lauryl chloride, and polyethylene glycol that self-assemble into 15-20 nm nanoparticles. Investigators at Rutgers University (Piscataway, NJ, USA) found that these molecules primarily targeted SR-A and CD36, the major macrophage scavenger receptors.

Scavenger receptors participate in the removal of foreign substances and waste materials in the living body by extensive ligand specificity and a variety of receptor molecules. In atherosclerotic lesions, macrophages that express scavenger receptors on their plasma membrane aggressively uptake the oxidized low-density lipoprotein (LDL) deposited in the blood vessel wall and become foam cells that secrete various inflammatory cytokines and accelerate the development of atherosclerosis.

Results published in the May 10, 2006, online edition of Biomacromolecules revealed that the micellar configuration of the nanoblockers and the combined display of anionic groups in their hydrophobic region caused the most effective inhibition in the uptake of oxidized LDL by IC21 macrophages.

Contributing author Dr. Kathryn Uhrich, professor of chemistry and chemical biology at Rutgers University, said, "We are employing the tools of nanotechnology--specifically tailoring the structure of the molecule, changing groups on the ends of the chains, and closely analyzing which forms of the particles bind to the different macrophage receptors. The significant finding of our study is that the nanoscale organization matters tremendously for blockage of oxidized LDL, which opens new avenues for more specific targeting of receptors.”



Related Links:
Rutgers University