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

IF 2.5 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology and Bioprocess Engineering Pub Date : 2024-04-10 DOI:10.1007/s12257-024-00101-w

Woojeong Lee, Yong Geun Lim, Yeong Jun Song, Kyeongsoon Park

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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 lipid-laden foam cells provides a promising prevention strategy in the progression of atherosclerotic plaques.

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甘露糖-β-环糊精共轭物对胆固醇载脂泡沫细胞的细胞内胆固醇外流作用

动脉壁内的载脂泡沫细胞在疾病早期动脉粥样硬化病变的发展过程中起着关键作用，它们已被认为是开发动脉粥样硬化靶向治疗药物的诱人靶点。在此，我们开发了甘露糖共轭β-环糊精（MAN-βCD），并评估了其对富含胆固醇的泡沫细胞的靶向能力和细胞内胆固醇外流情况。合成的 MAN-βCD 在水溶液条件下显示出有效的胆固醇提取能力。无毒且与细胞相容的MAN-βCD可特异性地靶向CD206阳性表达的富含胆固醇的泡沫细胞，并通过受体介导的内吞作用被细胞内化。此外，内化的 MAN-βCD 还能有效减少富含胆固醇的泡沫细胞内的脂滴（LD），从而显著防止 LD 的积累。因此，将MAN-βCD特异性地输送到表达CD206的脂质负载泡沫细胞中，为动脉粥样硬化斑块的进展提供了一种很有前景的预防策略。

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来源期刊

Biotechnology and Bioprocess Engineering 工程技术-生物工程与应用微生物

CiteScore

5.00

自引率

12.50%

发文量

审稿时长

3 months

期刊介绍： Biotechnology and Bioprocess Engineering is an international bimonthly journal published by the Korean Society for Biotechnology and Bioengineering. BBE is devoted to the advancement in science and technology in the wide area of biotechnology, bioengineering, and (bio)medical engineering. This includes but is not limited to applied molecular and cell biology, engineered biocatalysis and biotransformation, metabolic engineering and systems biology, bioseparation and bioprocess engineering, cell culture technology, environmental and food biotechnology, pharmaceutics and biopharmaceutics, biomaterials engineering, nanobiotechnology, and biosensor and bioelectronics.