A metal-organic framework-based immunomodulatory nanoplatform for anti-atherosclerosis treatment

Zhijue Xu; Zhaoyu Wu; Sheng Huang; Kaichuang Ye; Yihong Jiang; Jianqiang Liu; Junchao Liu; Xinwu Lu; Bo Li

doi:10.1016/j.jconrel.2023.01.024

A metal-organic framework-based immunomodulatory nanoplatform for anti-atherosclerosis treatment

J Control Release. 2023 Feb:354:615-625. doi: 10.1016/j.jconrel.2023.01.024. Epub 2023 Jan 23.

Authors

Zhijue Xu¹, Zhaoyu Wu¹, Sheng Huang¹, Kaichuang Ye², Yihong Jiang¹, Jianqiang Liu³, Junchao Liu¹, Xinwu Lu⁴, Bo Li⁵

Affiliations

¹ Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
² Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: ykaichuang@163.com.
³ The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China; Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Guangdong Medical University Key Laboratory of Research and Development of New Medical Materials, Dongguan 523808, China. Electronic address: jianqiangliu8@gdmu.edu.cn.
⁴ Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: luxinwu@shsmu.edu.cn.
⁵ Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: boli@shsmu.edu.cn.

PMID: 36641123
DOI: 10.1016/j.jconrel.2023.01.024

Abstract

Immunomodulatory therapy has become a promising method for the clinical treatment of many diseases. Recently, pilot studies revealed that immunomodulatory therapy exhibited good effects on the treatment of cardiovascular diseases, but many problems remain to be solved, such as useful platforms for drug co-delivery and combination therapies. In this study, we designed and constructed the multifunctional nanoparticle Rapa@UiO-66-NH-FAM-IL-1Ra (RUFI) for the treatment of atherosclerotic cardiovascular disease. This nanoplatform combined the advantages of metal-organic frameworks (MOFs) for drug co-delivery, rapamycin and IL-1Ra for immunomodulation, IL-1Ra for cellular targeting, and 5-FAM for fluorescence imaging. RUFI exhibited good drug release of rapamycin and IL-1Ra and specific cytotoxicity for inflammatory macrophages in vitro. In an atherosclerotic model of diet-fed ApoE^-/- mice, RUFI significantly targeted and reduced atherosclerosis plaques in coronary arteries, carotid arteries, and aortas. Mechanistic studies indicated that RUFI modulated macrophage phenotype, cytokine expression, and autophagy. This study demonstrated that combination therapy with rapamycin and IL-1Ra via MOF carriers enhanced the immunoregulatory effects against atherosclerosis. This drug co-delivery system suggests that MOF carriers loaded with immunomodulators are promising treatments for atherosclerosis or other inflammatory diseases.

Keywords: Cardiovascular disease; IL-1Ra; Immunomodulatory therapy; Metal-organic framework; Rapamycin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Atherosclerosis* / drug therapy
Interleukin 1 Receptor Antagonist Protein / genetics
Interleukin 1 Receptor Antagonist Protein / metabolism
Interleukin 1 Receptor Antagonist Protein / therapeutic use
Metal-Organic Frameworks*
Mice
Plaque, Atherosclerotic* / drug therapy
Sirolimus

Substances

Interleukin 1 Receptor Antagonist Protein
Metal-Organic Frameworks
Sirolimus