Hybrid Aptamer Molecularly Imprinted Polymer Nanoparticles for Reducing Oxidized Low-Density Lipoprotein Internalization by Macrophages

Oxidized low-density lipoprotein (oxLDL) is the most typical physiological trigger for the formation of macrophage foam cells, leading to atherosclerosis and coronary heart disease. The inhibition of internalized oxLDL in macrophages is a proven effective strategy for the prevention of atherosclerosis. A hybrid aptamer-molecularly imprinted polymer nanoparticle (AP-MIP NP) is a novel synthetic, biocompatible, selective material that can bind directly to oxLDL and decrease its uptake by macrophages by 62 ± 2% compared to oxLDL alone at a concentration of 8.25 × 10⁷ particles/mL. Oil red O staining indicates that macrophages treated with a combination of AP-MIP NP and oxLDL exhibited a marked decrease in intracellular lipid accumulation compared to those treated with oxLDL alone, resulting in reduced foam cell formation and a decrease in the production of tumor necrosis factor-α and interleukin-6 inflammatory cytokines. The polymer nanoparticle matrix effectively serves as a protective shell for the aptamer at hazardous pH conditions of 4.0 and 10.0, as well as in the presence of DNase I at 100 Kunitz units. The AP-MIP NP bound to the oxLDL surface disrupts the interaction between oxLDL and the lectin-like oxLDL receptor-1 and the cluster of differentiation 36 scavenger receptors, as demonstrated by receptor-coupled ELISA. This restricts the ability of macrophages to uptake oxLDL. This hybrid AP-MIP NP shows promise as a future therapeutic agent to reduce oxLDL uptake and inhibit foam cell formation for atherosclerosis prevention.