Intracellular cholesterol efflux effects of mannose-beta cyclodextrin conjugates on cholesterol-laden foam cells

Abstract

Lipid-laden foam cells within the arterial walls play a key role in the development of atherosclerotic lesions at early disease stages, and they have been recognized as attractive targets for developing targeted therapeutics in atherosclerosis. Herein, we developed mannose-conjugated beta-cyclodextrin (MAN-beta CD) and evaluated its targeting ability and intracellular cholesterol efflux toward cholesterol-laden foam cells. The synthesized MAN-beta CD showed effective cholesterol extraction ability in aqueous conditions. The nontoxic and cytocompatible MAN-beta CD specifically targeted cholesterol-laden foam cells with positive CD206 expressions and was internalized into the cells via receptor-mediated endocytosis. Additionally, the internalized MAN-beta CD exhibited effective lipid droplet (LD) reduction within the cholesterol-laden foam cells, leading to remarkable prevention of LD accumulation. Therefore, the specific delivery of MAN-beta CD into CD206-expressing lipid-laden foam cells provides a promising prevention strategy in the progression of atherosclerotic plaques.