Biomimetic nanoparticles to enhance the reverse cholesterol transport for selectively inhibiting development into foam cell in atherosclerosis

作者全名："Zhu, Li; Li, Hongjiao; Li, Jiyu; Zhong, Yuan; Wu, Shuai; Yan, Meng; Ni, Sheng; Zhang, Kun; Wang, Guixue; Qu, Kai; Yang, Deqin; Qin, Xian; Wu, Wei"

作者地址："[Zhu, Li; Li, Jiyu; Zhong, Yuan; Wu, Shuai; Yan, Meng; Ni, Sheng; Zhang, Kun; Wang, Guixue; Qu, Kai; Qin, Xian; Wu, Wei] Chongqing Univ, Key Lab Biorheol Sci & Technol, State & Local Joint Engn Lab Vasc Implants, Minist Educ,Bioengn Coll, Chongqing 400044, Peoples R China; [Li, Hongjiao; Yang, Deqin] Chongqing Med Univ, Sch & Hosp Stomatol, Chongqing 404100, Peoples R China; [Zhang, Kun; Qu, Kai; Qin, Xian] Chongqing Univ, Three Gorges Hosp, Chongqing 404000, Peoples R China; [Wang, Guixue; Wu, Wei] Jin Feng Lab, Chongqing 401329, Peoples R China"

通信作者："Qu, K; Qin, X; Wu, W (通讯作者)，Chongqing Univ, Key Lab Biorheol Sci & Technol, State & Local Joint Engn Lab Vasc Implants, Minist Educ,Bioengn Coll, Chongqing 400044, Peoples R China.; Yang, DQ (通讯作者)，Chongqing Med Univ, Sch & Hosp Stomatol, Chongqing 404100, Peoples R China.; Qu, K; Qin, X (通讯作者)，Chongqing Univ, Three Gorges Hosp, Chongqing 404000, Peoples R China.; Wu, W (通讯作者)，Jin Feng Lab, Chongqing 401329, Peoples R China."

来源：JOURNAL OF NANOBIOTECHNOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001057674000001

JCR分区：Q1

影响因子：10.6

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Biomimetic nanoparticles; Atherosclerosis; Macrophage membrane; Methotrexate; Cholesterol efflux; Target delivery

摘要："A disorder of cholesterol homeostasis is one of the main initiating factors in the progression of atherosclerosis (AS). Metabolism and removal of excess cholesterol facilitates the prevention of foam cell formation. However, the failure of treatment with drugs (e.g. methotrexate, MTX) to effectively regulate progression of disease may be related to the limited drug bioavailability and rapid clearance by immune system. Thus, based on the inflammatory lesion ""recruitment"" properties of macrophages, MTX nanoparticles (MTX NPs) camouflaged with macrophage membranes (MM@MTX NPs) were constructed for the target to AS plaques. MM@MTX NPs exhibited a uniform hydrodynamic size around similar to 360 nm and controlled drug release properties (similar to 72% at 12 h). After the macrophage membranes (MM) functionalized ""homing"" target delivery to AS plaques, MM@MTX NPs improved the solubility of cholesterol by the functionalized ss-cyclodextrin (ss-CD) component and significantly elevate cholesterol efflux by the loaded MTX mediated the increased expression levels of ABCA1, SR-B1, CYP27A1, resulting in efficiently inhibiting the formation of foam cells. Furthermore, MM@MTX NPs could significantly reduce the area of plaque, aortic plaque and cholesterol crystals deposition inApoE-/- mice and exhibited biocompatibility. It is suggested that MM@MTX NPs were a safe and efficient therapeutic platform for AS."

基金机构："This work was supported by grants from the National Natural Science Foundation of China (31971301, 32171324), Fundamental Research Funds for the National Key Ramp;amp;D Project (2022YFF0710700), Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0 [32171324, 2022YFF0710700]; National Natural Science Foundation of China [cstc2021jcyj-msxmX0149]; Fundamental Research Funds for the National Key Ramp;amp;D Project [2022M710526]; Natural Science Foundation of Chongqing [2022M720574, 2022CDJXY-026]; Postdoctoral Research Foundation of China [2020CDJQY-A061, 2018CDHB1B08, jfkyjf202203001]; Fundamental Research Funds for Central Universities; JinFeng Laboratory of Chongqing; [31971301]"

基金资助正文："This work was supported by grants from the National Natural Science Foundation of China (31971301, 32171324), Fundamental Research Funds for the National Key R&D Project (2022YFF0710700), Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0149), Postdoctoral Research Foundation of China (2022M710526, 2022M720574), Fundamental Research Funds for Central Universities (2022CDJXY-026, 2020CDJQY-A061, 2018CDHB1B08), JinFeng Laboratory of Chongqing (jfkyjf202203001). In addition, we would like to thank Mr. Zhang Bin at Analytical and Testing Center of Chongqing University for their assistance with TEM."