In the progression of acute inflammation, the activation and recruitment of macrophages and neutrophils are mutually reinforcing, leading to amplified inflammatory response and severe tissue damage. Therefore, to regulate the axis of neutrophils and macrophages is essential to avoid tissue damage induced from acute inflammatory. Apoptotic neutrophils can regulate the anti-inflammatory activity of macrophages through the efferocytosis. The strategy of targeting and inducing neutrophil apoptosis has the potential to modulate macrophage activity and transfer anti-inflammatory drugs. Herein, a natural glycyrrhiza protein nanoparticle loaded with dexamethasone (Dex@GNPs) was constructed, which could simultaneously regulate neutrophil and macrophage function during acute inflammation treatment by combining neutrophil apoptosis and macrophage efferocytosis. Dex@GNPs can be rapidly and selectively internalized by neutrophils and subsequently induce neutrophils apoptosis through a ROS-dependent mechanism. The efferocytosis of apoptotic neutrophils not only promoted the polarization of macrophages into anti-inflammatory state, but also facilitated the transfer of Dex@GNPs to macrophages. This enabled dexamethasone to further modulate macrophage function. In mouse models of acute respiratory distress syndrome and sepsis, Dex@GNPs significantly ameliorated the disordered immune microenvironment and alleviated tissue injury. This study presents a novel strategy for drug delivery and inflammation regulation to effectively treat acute inflammatory diseases.

中文翻译：

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甘草蛋白纳米粒子介导的原位中性粒细胞凋亡和巨噬细胞胞吞作用用于急性炎症治疗

在急性炎症的进展中，巨噬细胞和中性粒细胞的激活和募集是相辅相成的，导致炎症反应放大和严重的组织损伤。因此，调节中性粒细胞和巨噬细胞的轴对于避免急性炎症引起的组织损伤至关重要。凋亡的中性粒细胞可以通过胞吞作用调节巨噬细胞的抗炎活性。靶向和诱导中性粒细胞凋亡的策略具有调节巨噬细胞活性和转移抗炎药物的潜力。在此，构建了一种负载地塞米松的天然甘草蛋白纳米颗粒（Dex@GNPs），通过结合中性粒细胞凋亡和巨噬细胞胞吞作用，在急性炎症治疗过程中同时调节中性粒细胞和巨噬细胞功能。 Dex@GNPs 可以快速、选择性地被中性粒细胞内化，随后通过 ROS 依赖性机制诱导中性粒细胞凋亡。凋亡中性粒细胞的胞吞作用不仅促进巨噬细胞极化进入抗炎状态，而且有利于Dex@GNPs向巨噬细胞的转移。这使得地塞米松能够进一步调节巨噬细胞功能。在急性呼吸窘迫综合征和脓毒症小鼠模型中，Dex@GNPs 显着改善紊乱的免疫微环境并减轻组织损伤。这项研究提出了一种药物输送和炎症调节的新策略，以有效治疗急性炎症性疾病。