Posted by 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. Efferocytosis is the mechanism used by macrophages to efficiently clear apoptotic cell and inflammatory mediators for ameliorating inflammation as well as stabilizing plaque. Herein, a sequential-targeting nanoplatform (HT-rHDL reconstituted high desity lipoprotein) 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 β-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 3-month 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.
Yanyan Wang, Hai Gao, Xinya Huang, Zhaoan Chen, Pengyu Kang, Yunyi Zhou, Danhua Qin, Wenli Zhang, Jianping Liu (2022) Cyclodextrin boostered-high density lipoprotein for antiatherosclerosis by regulating cholesterol efflux and efferocytosis. Carbohydrate Polymers 292, 119632
https://doi.org/10.1016/j.carbpol.2022.119632.