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使用负载肝X受体激动剂的纳米载体靶向动脉粥样硬化中的巨噬细胞:一篇综述

Targeting macrophages in atherosclerosis using nanocarriers loaded with liver X receptor agonists: A narrow review.

作者信息

Yang Tong-Mei, Miao Miao, Yu Wen-Qian, Wang Xue, Xia Fang-Jie, Li Yan-Jie, Guo Shou-Dong

机构信息

Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang, China.

出版信息

Front Mol Biosci. 2023 Mar 2;10:1147699. doi: 10.3389/fmolb.2023.1147699. eCollection 2023.

Abstract

Macrophages are involved in the whole process of atherosclerosis, which is characterized by accumulation of lipid and inflammation. Presently, clinically used lipid-lowering drugs cannot completely retard the progress of atherosclerosis. Liver X receptor (LXR) plays a key role in regulation of lipid metabolism and inflammation. Accumulating evidence have demonstrated that synthetic LXR agonists can significantly retard the development of atherosclerosis. However, these agonists induce sever hypertriglyceridemia and liver steatosis. These side effects have greatly limited their potential application for therapy of atherosclerosis. The rapid development of drug delivery system makes it possible to delivery interested drugs to special organs or cells using nanocarriers. Macrophages express various receptors which can recognize and ingest specially modified nanocarriers loaded with LXR agonists. In the past decades, a great progress has been made in this field. These macrophage-targeted nanocarriers loaded with LXR agonists are found to decrease atherosclerosis by reducing cholesterol accumulation and inflammatory reactions. Of important, these nanocarriers can alleviate side effects of LXR agonists. In this article, we briefly review the roles of macrophages in atherosclerosis, mechanisms of action of LXR agonists, and focus on the advances of macrophage-targeted nanocarriers loaded with LXR agonists. This work may promote the potential clinical application of these nanocarriers.

摘要

巨噬细胞参与动脉粥样硬化的全过程,其特征为脂质积聚和炎症。目前,临床使用的降脂药物不能完全延缓动脉粥样硬化的进展。肝脏X受体(LXR)在脂质代谢和炎症调节中起关键作用。越来越多的证据表明,合成LXR激动剂可显著延缓动脉粥样硬化的发展。然而,这些激动剂会引发严重的高甘油三酯血症和肝脂肪变性。这些副作用极大地限制了它们在动脉粥样硬化治疗中的潜在应用。药物递送系统的快速发展使得利用纳米载体将感兴趣的药物递送至特定器官或细胞成为可能。巨噬细胞表达多种受体,这些受体可识别并摄取装载有LXR激动剂的特殊修饰纳米载体。在过去几十年中,该领域取得了巨大进展。发现这些装载有LXR激动剂的巨噬细胞靶向纳米载体可通过减少胆固醇积聚和炎症反应来减轻动脉粥样硬化。重要的是,这些纳米载体可减轻LXR激动剂的副作用。在本文中,我们简要综述了巨噬细胞在动脉粥样硬化中的作用、LXR激动剂的作用机制,并重点介绍了装载有LXR激动剂的巨噬细胞靶向纳米载体的研究进展。这项工作可能会促进这些纳米载体的潜在临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/235e/10018149/6d073a0d1610/fmolb-10-1147699-g001.jpg

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