期刊
CARBOHYDRATE POLYMERS
卷 292, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2022.119632
关键词
Atherosclerosis; LXR activation; Cholesterol efflux; Efferocytosis; Hyaluronan; Sequential-targeting; Reconstituted high-density lipoprotein; ?-Cyclodextrin
资金
- National Natural Science Foundation of China [81773669]
- National Major Science and Technology Project of China [2017YFA0205400]
- Graduate Cultivation Innovative Project of Jiangsu Province [KYCX20-0624]
This study designed a sequential-targeting nanoplatform for the treatment of atherosclerosis. The nanoplatform can release specific drugs in atherosclerotic macrophages to achieve therapeutic effects.
A promising therapy for atherosclerosis treatment was designed by targeting LXR receptor (LXR) on atherosclerotic macrophage, where LXR activation could regulate cholesterol efflux and efferocytosis. Herein, a sequential-targeting nanoplatform (HT-rHDL) was constructed to deliver LXR agonist into macrophage, which was composed of discoidal reconstituted high-density lipoprotein (d-rHDL) core for agonist encapsulation and external modifications: (i) the outermost hyaluronan, targeting injured endothelium; (ii) modified beta-cyclodextrin of d-rHDL, accelerating cholesterol efflux of foam cells; (iii) conjugated apolipoprotein A-I of d-rHDL, targeting macrophage. This design underlines that the nanoplatform could increase its plaque accumulation, accomplish cholesterol efflux-remodeling-drug delivery behavior and specifically activate LXR in macrophage. After a 3month treatment with HT-rHDL, 31.47% plaque area reduction, 56.0% lipid accumulation decrease, obvious inflammation resolution and enhanced plaque stability were observed. Furthermore, the atherosclerosis intervention was demonstrated to benefit from the upregulations of ABC transporters and Mer tyrosine kinase. Collectively, HT-rHDL provides new strategies to regress atherosclerosis.
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