Citation: Xueyi Weng, Weiyan Li, Haipeng Tan, Zhiqing Pang, Jinfeng Gao, Shiteng Cai, Jing Chen, Qiaozi Wang, Qiyu Li, Youran Li, Hongbo Yang, Zhengmin Wang, Yiwen Tan, Yuyuan Fu, Chengzhi Han, Zheyong Huang, Yanan Song, Junbo Ge, Juying Qian. Engineered macrophage membrane fusion liposomes carrying siRNA for spatiotemporal regulation of the CCL2/CCR2 axis for cardiac repair[J]. Chinese Chemical Letters, ;2026, 37(7): 111666. doi: 10.1016/j.cclet.2025.111666 shu

Engineered macrophage membrane fusion liposomes carrying siRNA for spatiotemporal regulation of the CCL2/CCR2 axis for cardiac repair

Xueyi Weng ^{a, b, c, d, 1} ,
Weiyan Li ^{b, c, d, 1} ,
Haipeng Tan ^{e, f, 1} ,
Zhiqing Pang ^{g, 1} ,
Jinfeng Gao ^{b, c, d} ,
Shiteng Cai ^{b, c, d} ,
Jing Chen ^{b, c, d} ,
Qiaozi Wang ^{b, c, d} ,
Qiyu Li ^{b, c, d} ,
Youran Li ^{b, c, d} ,
Hongbo Yang ^{b, c, d} ,
Zhengmin Wang ^{b, c, d} ,
Yiwen Tan ^{b, c, d} ,
Yuyuan Fu ^{b, c, d} ,
Chengzhi Han ^{b, c, d} ,
Zheyong Huang ^{b, c, d, *,} ,
Yanan Song ^{b, c, d, *,} ,
Junbo Ge ^{b, c, d} ,
Juying Qian ^{a, b, c, d, *,}

a.
Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China
b.
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China
c.
National Clinical Research Center for Interventional Medicine, Shanghai 200032, China
d.
Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai 200032, China
e.
Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
f.
Cardiovascular Disease Laboratory of Chongqing Medical University, Chongqing 400016, China
g.
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201210, China

zheyonghuang@126.com

yanan.song@163.com

Qian.juying@zs-hospital.sh.cn

Received Date: 15 April 2025
Revised Date: 30 July 2025
Accepted Date: 31 July 2025
Available Online: 5 August 2025

Figures(4)

Excessive and prolonged inflammatory monocyte activity accelerates left ventricular remodeling after myocardial infarction (MI). After myocardial reperfusion, the CCL2/CCR2 axis is considered to be a key chemokine axis that initiates and modulates tissue inflammatory damage. Effectively blocking the CCL2/CCR2 axis can reduce the chemotaxis of inflammatory monocytes to the infarct area, which has important therapeutic value for the repair of myocardium after reperfusion injury (MI/R). Here, we propose a nanoparticle carrying CCL2 silencing short interfering RNA (siRNA), which is prepared by coating a lipid hybrid CCR2-overexprssion macrophage cell membrane on a siRNA-loaded mesoporous silica nanoparticle. The overexpression of CCR2 and adhesion factors on the macrophage membrane improves its targeting ability, directing nanoparticle to the myocardial infarction area of MI/R-induced mice, the overexpress CCR2 in the macrophage cell membrane also adsorb more CCL2. Then by fusing with the cell membrane, siRNA is released into the injured endothelial cells cytoplasm, silencing the expression of CCL2. In vivo administration of the formula blocked CCL2/CCR2 axis, reduce the chemotaxis of inflammatory cells, regulate the immune microenvironment, further decreasing myocardial infarction area and improving cardiac function. Targeted block of CCL2/CCR2 axis represent a new therapeutic intervention for inflammatory disease.
- CCL2/CCR2 axis,
- Spatiotemporal regulation,
- siRNA delivery,
- Macrophages,
- Myocardial ischemia-reperfusion injury
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