Engineered neutrophil apoptotic bodies ameliorate myocardial infarction by promoting macrophage efferocytosis and inflammation resolution

Abstract

Inflammatory response plays a critical role in myocardial infarction (MI) repair. The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration, while the therapeutic strategy that simulates and enhances this natural process has not been established. Here, we constructed engineered neutrophil apoptotic bodies (eNABs) to simulate natural neutrophil apoptosis, which regulated inflammation response and enhanced MI repair. The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties, and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride (HAL). The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release, thereby further enhancing the anti-inflammation effects. In in vivo studies, the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function. This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.

New diagnostic and therapeutic strategies for myocardial infarction via nanomaterials

“… 114 Inspired by this phenomenon, Bao et al. 115 fused the natural membrane of neutrophil apoptotic bodies with hexyl 5-aminolevulinate hydrochloride (HAL) preloaded mesoporous silica to synthesize nanoparticles (MSN-HAL) and proved that macrophages could uptake them, degrading the mesoporous silica to release the inner HAL that produced bilirubin, an anti-inflammatory metabolite intracellularly. After LAD ligation followed by three-day tail vein injection of nanoparticles, given to the CD11b, CD44, and αLβ2-integrin combined on the surface of apoptotic bodies, the nanoparticles had the capability to target cardiac inflammation actively, thus promoting the M2 polarization and improving cardiac functions.…”

Exosome-Based Treatment for Atherosclerosis

“…The FDA-approved hexyl 5-aminolevulinate hydrochloride (HAL) is known to have anti-inflammatory effects by initiating the biosynthesis of anti-inflammatory bilirubin [91][92][93]. Wu et al, generated M2 macrophage-derived exosomes, showing intrinsic inflammation-tropism capability, loaded with HAL (HAL@M2 exosomes) by electroporation and tested their effect on atherosclerosis [94].…”

Advances in the Therapeutic Effects of Apoptotic Bodies on Systemic Diseases

“…Chimeric ApoBDs functionalized with a natural membrane and modular delivery system can be applied for the modulation of inflammation [ 104 ]. The combination of natural neutrophils and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride (HAL) exhibited excellent inflammation-tropism and immunoregulatory properties in myocardial infarction [ 105 ].…”