Biotechnology and Bioprocess Engineering 2024; 29(3): 483-493  
Intracellular cholesterol efflux effects of mannose-beta cyclodextrin conjugates on cholesterol-laden foam cells
Woojeong Lee1 · Yong Geun Lim1 · Yeong Jun Song1 · Kyeongsoon Park1
1 Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Korea
Correspondence to: Kyeongsoon Park
kspark1223@cau.ac.kr
Received: December 4, 2023; Revised: March 26, 2024; Accepted: April 1, 2024; Published online: April 10, 2024.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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-βCD) and evaluated its targeting ability and intracellular cholesterol efflux toward cholesterol-laden foam cells. The synthesized MAN-βCD showed effective cholesterol extraction ability in aqueous conditions. The nontoxic and cytocompatible MAN-βCD specifically targeted cholesterol-laden foam cells with positive CD206 expressions and was internalized into the cells via receptor-mediated endocytosis. Additionally, the internalized MAN-βCD 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-βCD into CD206-expressing lipidladen foam cells provides a promising prevention strategy in the progression of atherosclerotic plaques.
Keywords: Mannose · Beta-cyclodextrin · Targeted delivery · CD206 · Cholesterol-laden foam cells

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