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

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

doi:10.1186/s12951-023-02040-9

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

J Nanobiotechnology. 2023 Aug 29;21(1):307. doi: 10.1186/s12951-023-02040-9.

Authors

Li Zhu¹, Hongjiao Li², Jiyu Li¹, Yuan Zhong¹, Shuai Wu¹, Meng Yan¹, Sheng Ni¹, Kun Zhang^{1

3}, Guixue Wang^{1

4}, Kai Qu^{5

6}, Deqin Yang⁷, Xian Qin^{8

9}, Wei Wu^{10

11}

Affiliations

¹ Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China.
² School and Hospital of Stomatology, Chongqing Medical University, Chongqing, 404100, China.
³ Chongqing University, Three Gorges Hospital, Chongqing, 404000, China.
⁴ Jin Feng Laboratory, Chongqing, 401329, China.
⁵ Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China. qukaigood@qq.com.
⁶ Chongqing University, Three Gorges Hospital, Chongqing, 404000, China. qukaigood@qq.com.
⁷ School and Hospital of Stomatology, Chongqing Medical University, Chongqing, 404100, China. yangdeqin@hospital.cqmu.edu.cn.
⁸ Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China. qinxian224@cqu.edu.cn.
⁹ Chongqing University, Three Gorges Hospital, Chongqing, 404000, China. qinxian224@cqu.edu.cn.
¹⁰ Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China. david2015@cqu.edu.cn.
¹¹ Jin Feng Laboratory, Chongqing, 401329, China. david2015@cqu.edu.cn.

Abstract

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 ~ 360 nm and controlled drug release properties (~ 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 β-cyclodextrin (β-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 in ApoE^-/- mice and exhibited biocompatibility. It is suggested that MM@MTX NPs were a safe and efficient therapeutic platform for AS.

Keywords: Atherosclerosis; Biomimetic nanoparticles; Cholesterol efflux; Macrophage membrane; Methotrexate; Target delivery.

MeSH terms

Animals
Atherosclerosis* / drug therapy
Biological Transport
Biomimetics
Foam Cells
Mice
Plaque, Atherosclerotic*

Abstract

MeSH terms

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