title: TARGETING OF MACROPHAGE FOAM CELLS IN ATHEROSCLEROTIC PLAQUE USING OLIGONUCLEOTIDE-FUNCTIONALIZED NANOPARTICLES.
abstract: Macrophage foam cells are key components of atherosclerotic plaque and play an important role in the progression of atherosclerosis leading to plaque rupture and thrombosis. Foam cells are emerging as attractive targets for therapeutic intervention and for imaging the progression of disease. Therefore, designing nanoparticles (NPs) targeted to macrophage foam cells in plaque is of considerable therapeutic significance. Here we report the construction of an oligonucleotide functionalized NP system with high affinity for foam cells. Nanoparticles functionalized with a 23-mer poly-Guanine (polyG) oligonucleotide are specifically recognized by the scavenger receptors on lipid-laden foam cells in vitro and ex vivo. The enhanced uptake of polyG-functionalized NPs by foam cells is inhibited in the presence of acetylated-LDL, a known ligand of scavenger receptors. Since polyG oligonucleotides are stable in serum and are unlikely to induce an immune response, their use for scavenger receptor-mediated targeting of macrophage foam cells provides a strategy for targeting atherosclerotic lesions.
authors.affiliation: Program for Excellence in Nanomedicine, Sanford-Burnham Medical Research Institute 10901 N. Torrey Pines Road, La Jolla, CA, USA 92037.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Sharma
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: She
authors.forename: David T
authors.initials: DT
authors.lastname: Valenta
authors.forename: William B
authors.initials: WB
authors.lastname: Stallcup
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Smith