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.

炎症反应在心肌梗塞 (MI) 修复中起着关键作用。中性粒细胞凋亡和随后的巨噬细胞摄入可导致炎症消退并启动再生，而模拟和增强这种自然过程的治疗策略尚未建立。在这里，我们构建了工程中性粒细胞凋亡小体 (eNABs) 来模拟天然中性粒细胞凋亡，从而调节炎症反应和增强 MI 修复。eNABs 是通过将具有优异炎症趋向性和免疫调节特性的天然中性粒细胞凋亡体膜和负载有 5-氨基乙酰丙酸己酯盐酸盐 (HAL) 的介孔二氧化硅纳米颗粒相结合而制成的。主动靶向巨噬细胞的eNABs和包裹的HAL同时启动血红素的生物合成途径，细胞内释放后产生抗炎胆红素，从而进一步增强抗炎作用。在在体内研究中，eNABs 有效地调节梗塞区域的炎症反应以改善心脏功能。该研究展示了一种有效的仿生构建策略，可以调节巨噬细胞功能以进行 MI 修复。