Neutrophil membrane-camouflaged nanoparticles alleviate inflammation and promote angiogenesis in ischemic myocardial injury

Dongjian Han; Fuhang Wang; Zhentao Qiao; Bo Wang; Yi Zhang; Qingjiao Jiang; Miaomiao Liu; Yuansong Zhuang; Quanxu An; Yan Bai; Jiahong Shangguan; Jinying Zhang; Gaofeng Liang; Deliang Shen

doi:10.1016/j.bioactmat.2022.11.016

Neutrophil membrane-camouflaged nanoparticles alleviate inflammation and promote angiogenesis in ischemic myocardial injury

Bioact Mater. 2022 Nov 28:23:369-382. doi: 10.1016/j.bioactmat.2022.11.016. eCollection 2023 May.

Authors

Dongjian Han^{1

2}, Fuhang Wang^{1

2}, Zhentao Qiao³, Bo Wang^{1

2}, Yi Zhang^{1

2}, Qingjiao Jiang^{1

2}, Miaomiao Liu^{1

2}, Yuansong Zhuang^{1

2}, Quanxu An^{1

2}, Yan Bai^{1

2}, Jiahong Shangguan^{1

2}, Jinying Zhang^{1

2}, Gaofeng Liang⁴, Deliang Shen^{1

2}

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
² Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, China.
³ Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
⁴ School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, Henan, China.

Abstract

Acute myocardial infarction (AMI) induces a sterile inflammatory response, leading to cardiomyocyte damage and adverse cardiac remodeling. Interleukin-5 (IL-5) plays an essential role in developing eosinophils (EOS), which are beneficial for the resolution of inflammation. Furthermore, the proangiogenic properties of IL-5 also contribute to tissue healing following injury. Therefore, targeted delivery of IL-5 is an innovative therapeutic approach for treating AMI. It has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug overdose. In this study, we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic membrane. The administration of neutrophil membrane-camouflaged nanoparticles (NM-NP_IL-5) in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium, thereby limiting adverse cardiac remodeling after AMI. Our results also demonstrated that the NM-NP_IL-5 could serve as neutrophil "decoys" to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their "parent" neutrophils. Finally, the targeted delivery of NM-NP_IL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function. Our findings provided a promising cardiac detoxification agent for acute cardiac injury.

Keywords: Angiogenesis; Biomimetic nanoparticles; Eosinophils; Interleukin-5; Myocardial infarction.