SCAVENGER RECEPTOR-MEDIATED 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 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, they are a promising candidate for developing an NP platform for scavenger receptor-mediated targeting of macrophages that can be optimized for targeting foam cells in atherosclerotic lesions.