Bao Lili, Dou Geng, Tian Ran, Lv Yajie, Ding Feng, Liu Siying, Zhao Ruifeng, Zhao Lu, Zhou Jun, Weng Lin, Dong Yan, Li Bei, Liu Shiyu, Chen Xin, Jin Yan
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi'an Jiao Tong University, Xi'an, 710049, China.
Bioact Mater. 2021 Aug 27;9:183-197. doi: 10.1016/j.bioactmat.2021.08.008. eCollection 2022 Mar.
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 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.
炎症反应在心肌梗死（MI）修复中起关键作用。中性粒细胞凋亡及随后的巨噬细胞吞噬可导致炎症消退并启动再生，然而模拟并增强这一自然过程的治疗策略尚未确立。在此，我们构建了工程化中性粒细胞凋亡小体（eNABs）以模拟天然中性粒细胞凋亡，其可调节炎症反应并增强MI修复。eNABs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小体膜与负载盐酸5-氨基乙酰丙酸己酯（HAL）的介孔二氧化硅纳米颗粒相结合制备而成。eNABs可主动靶向巨噬细胞，且包封的HAL在细胞内释放后可同时启动血红素的生物合成途径以产生抗炎胆红素，从而进一步增强抗炎作用。在研究中，eNABs有效调节梗死区域的炎症反应以改善心脏功能。本研究展示了一种有效的仿生构建策略，可调节巨噬细胞功能以促进MI修复。
