期刊
JOURNAL OF CONTROLLED RELEASE
卷 349, 期 -, 页码 2-15出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.06.053
关键词
Host -guest interaction; ?-Cyclodextrin; Drug delivery; Cell -based carriers; Atherosclerosis
资金
- Science and Technology Development Fund (FDCT) of Macau SAR [0065/2021/A2]
- Shenzhen Science and Technology Innovation Commission [SGDX20210823103803027]
- National Natural Science Foun-dation of China [22071275, 21871301, 32001016, 81903988]
This article introduces a method of targeted anti-atherosclerosis therapy using macrophage-liposome conjugate, which can lyse plaques, alleviate inflammation, and promote cholesterol efflux, effectively regressing atherosclerotic plaques.
Current pharmacological treatments of atherosclerosis often target either cholesterol control or inflammation management, to inhibit atherosclerotic progression, but cannot lead to direct plaque lysis and atherosclerotic regression, partly due to the poor accumulation of medicine in the atherosclerotic plaques. Due to enhanced macrophage recruitment during atheromatous plaque progression, a macrophage-liposome conjugate was facilely constructed for targeted anti-atherosclerosis therapy via synergistic plaque lysis and inflammation alleviation. Endogenous macrophage is utilized as drug-transporting cell, upon membrane-modification with a beta-cyclodextrin (beta-CD) derivative to form beta-CD decorated macrophage (CD-MP). Adamantane (ADA) modified quercetin (QT)-loaded liposome (QT-NP), can be conjugated to CD-MP via host-guest interactions between beta-CD and ADA to form macrophage-liposome conjugate (MP-QT-NP). Thus, macrophage carries liposome hand-inhand to significantly increase the accumulation of anchored QT-NP in the aorta plaque in response to the plaque inflammation. In addition to anti-inflammation effects of QT, MP-QT-NP efficiently regresses atherosclerotic plaques from both murine aorta and human carotid arteries via CD-MP mediated cholesterol efflux, due to the binding of cholesterol by excess membrane beta-CD. Transcriptome analysis of atherosclerotic murine aorta and human carotid tissues reveal that MP-QT-NP may activate NRF2 pathway to inhibit plaque inflammation, and simultaneously upregulate liver X receptor to promote cholesterol efflux.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据