Affinity-Driven Design of Cargo-Switching Nanoparticles to Leverage a Cholesterol-Rich Microenvironment for Atherosclerosis Therapy.
Affinity-Driven Design of Cargo-Switching Nanoparticles to Leverage a Cholesterol-Rich Microenvironment for Atherosclerosis Therapy.
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DOI：
10.1021/acsnano.9b08216
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发表时间：
2020-06-23
期刊：
影响因子：
17.1
通讯作者：
Park JH
中科院分区：
文献类型：
--
作者：
Kim H;Kumar S;Kang DW;Jo H;Park JH
动脉粥样硬化斑块表现出胆固醇和巨噬细胞的高沉积。这些不仅是斑块的主要成分，也是关键的炎症触发源。然而，没有现有的治疗方法可以实现有效去除斑块内的两种成分。在这里，我们报告了货物转换纳米颗粒（CSNP），其物理化学设计用于结合胆固醇并在斑块微环境中释放抗炎药物。CSNP具有核-壳结构，核由甲基-β-环糊精（环糊精）和辛伐他汀（他汀）的包合复合物组成，壳由磷脂组成。在与胆固醇（其对环糊精的亲和力高于他汀类药物）相互作用后，CSNP通过货物转换释放他汀类药物和胆固醇。CSNP在体外表现出对胆固醇敏感的多方面抗动脉粥样硬化功能，这归因于他汀类药物的释放和胆固醇的消耗。在动脉粥样硬化的小鼠模型中，全身注射的CSNP靶向动脉粥样硬化斑块并降低胆固醇和巨噬细胞的斑块含量，这协同导致有效预防动脉粥样硬化形成和已建立的斑块消退。这些发现表明，CSNP提供了一个治疗平台，与胆固醇相关的炎症性疾病，如动脉粥样硬化接口。
Atherosclerotic plaques exhibit high deposition of cholesterol and macrophages. These are not only the main components of the plaques but also key inflammation-triggering sources. However, no existing therapeutics can achieve effective removal of both components within the plaques. Here, we report cargo-switching nanoparticles (CSNP) that are physicochemically designed to bind to cholesterol and release anti-inflammatory drug in the plaque microenvironment. CSNP have a core–shell structure with a core composed of an inclusion complex of methyl-β-cyclodextrin (cyclodextrin) and simvastatin (statin), and a shell of phospholipids. Upon interaction with cholesterol, which has higher affinity to cyclodextrin than statin, CSNP release statin and scavenge cholesterol instead through cargo-switching. CSNP exhibit cholesterol-sensitive multifaceted antiatherogenic functions attributed to statin release and cholesterol depletion in vitro. In mouse models of atherosclerosis, systemically injected CSNP target atherosclerotic plaques and reduce plaque content of cholesterol and macrophages, which synergistically leads to effective prevention of atherogenesis and regression of established plaques. These findings suggest that CSNP provide a therapeutic platform for interfacing with cholesterol-associated inflammatory diseases such as atherosclerosis.
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DOI：
10.1161/atvbaha.116.307481
发表时间：
2016-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Gadde S;Rayner KJ
通讯作者：
Rayner KJ
影响因子：
5
作者：
Grebe, Alena;Latz, Eicke
通讯作者：
Latz, Eicke
DOI：
10.1016/j.jconrel.2015.08.050
发表时间：
2015-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Du J;Lane LA;Nie S
通讯作者：
Nie S
影响因子：
4.6
作者：
Brown A;Patel S;Ward C;Lorenz A;Ortiz M;DuRoss A;Wieghardt F;Esch A;Otten EG;Heiser LM;Korolchuk VI;Sun C;Sarkar S;Sahay G
通讯作者：
Sahay G
影响因子：
--
作者：
Akbarzadeh A;Rezaei-Sadabady R;Davaran S;Joo SW;Zarghami N;Hanifehpour Y;Samiei M;Kouhi M;Nejati-Koshki K
通讯作者：
Nejati-Koshki K