Abstract：
Acute lung injury (ALI) is a serious inflammatory disease that causes impairment of pulmonary function. Phenotypic modulation of macrophage in the lung using fibroblast growth factor 21 (FGF21) may be a potential strategy to alleviate lung inflammation. Consequently, achieving specific delivery of FGF21 to the inflamed lung and subsequent efficient FGF21 internalization by macrophages within the lung becomes critical for effective ALI treatment. Here, an apoptotic cell membrane-coated zirconium-based metal-organic framework UiO-66 is reported for precise pulmonary delivery of FGF21 (ACM@U-FGF21) whose design is inspired by the process of efferocytosis. ACM@U-FGF21 with apoptotic signals is recognized and internalized by phagocytes in the blood and macrophages in the lung, and then the intracellular ACM@U-FGF21 can inhibit the excessive secretion of pro-inflammatory cytokines by these cells to relieve the inflammation. Utilizing the homologous targeting properties inherited from the source cells and the spontaneous recruitment of immune cells to inflammatory sites, ACM@U-FGF21 can accumulate preferentially in the lung after injection. The results prove that ACM@U-FGF21 effectively reduces inflammatory damage to the lung by modulating lung macrophage polarization and suppressing the excessive secretion of pro-inflammatory cytokines by activated immune cells. This study demonstrates the usefulness of efferocytosis-inspired ACM@U-FGF21 in the treatment of ALI.
摘要：
急性肺损伤（ALI）是一种严重的炎症性疾病，可导致肺功能受损。使用成纤维细胞生长因子21（FGF21）对肺中巨噬细胞进行表型调节可能是减轻肺部炎症的潜在策略。因此,实现FGF21向发炎的肺的特异性递送以及随后由肺内的巨噬细胞进行的有效FGF21内化对于有效的ALI治疗是至关重要的。这里,我们报告了一种凋亡细胞膜涂覆的锆基金属有机框架UiO-66，用于FGF21（ACM@U-FGF21）的精确肺部递送，其设计受到了细胞增生过程的启发。具有凋亡信号的ACM@U-FGF21被血液中的吞噬细胞和肺中的巨噬细胞识别和内化，然后细胞内ACM@U-FGF21可以抑制这些细胞过度分泌促炎细胞因子以缓解炎症。利用源细胞遗传的同源靶向特性和免疫细胞自发募集到炎症部位，ACM@U-FGF21可以在注射后优先在肺中积累。结果证明ACM@U-FGF21通过调节肺巨噬细胞极化,抑制活化的免疫细胞过度分泌促炎细胞因子,从而有效减轻肺炎性损伤。这项研究证明了在ALI的治疗中，有效的细胞凋亡激发的ACM@U-FGF21。本文受版权保护。保留所有权利。
