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

Han, Dongjian; Wang, Fuhang; Qiao, Zhentao; Wang, Bo; Zhang, Yi; Jiang, Qingjiao; Liu, Miaomiao; Zhuang, Yuansong et al. · Bioact Mater · 2023

basic_science · Level V

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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<sub>IL-5</sub>) in the <i>in vivo</i> 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<sub>IL-5</sub> 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<sub>IL-5</sub> protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function. Our findings provided a promising cardiac detoxification agent for acute cardiac injury.