Fig. 1.

The envisioned paradigm to counteract atherosclerotic plaque development aims to repress lipid-scavenging receptors at the level of lesion-based macrophages. Sugar-based AMs were designed to competitively block oxLDL uptake via binding and regulation of SRs on human macrophages. A library of AMs, with systematic variations in charge, stereochemistry, and sugar backbones, was synthesized and kinetically fabricated into serum-stable, core/shell NPs and screened in vitro to identify shell architectures that exhibited maximal atheroprotective potency. To demonstrate lesion-level intervention, the lead NP was administered in an atherosclerosis animal model to challenge lesion development during coronary artery disease.