Polysalicylic Acid Polymer Microparticle Decoys Therapeutically Treat Acute Respiratory Distress Syndrome.
Polysalicylic Acid Polymer Microparticle Decoys Therapeutically Treat Acute Respiratory Distress Syndrome.
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聚水杨酸聚合物微粒诱饵可治疗急性呼吸窘迫综合征。
DOI：
10.1002/adhm.202101534
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发表时间：
2022-04
影响因子：
10
通讯作者：
Eniola-Adefeso O
中科院分区：
文献类型：
--
作者：
Brannon ER;Kelley WJ;Newstead MW;Banka AL;Uhrich KE;O'Connor CE;Standiford TJ;Eniola-Adefeso O
由于死亡率高且缺乏有效的治疗方法，急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）仍然存在问题。中性粒细胞损伤是ALI/ARDS死亡的重要原因。在这里，我们开发并评估了快速ARDS干预技术，其中静脉注射基于水杨酸的聚合物微粒，即，在ALI/ARDS小鼠模型中，聚阿司匹林（Poly-A）干扰血液中的中性粒细胞，减少肺中性粒细胞浸润和体内损伤。重要的是，在ARDS的活菌肺感染模型中，Poly-A颗粒减少了气道中的多种炎性细胞因子和血流中的细菌负荷，大大提高了生存率。我们观察到Poly-A微粒的吞噬作用，在聚合物骨架中含有水杨酸，改变了粘附分子的中性粒细胞表面表达，可能有助于其额外的治疗益处。鉴于微粒降解产物-水杨酸和己二酸-的已证实的安全性特征，我们预计Poly-A颗粒代表了ARDS的治疗策略，具有快速临床转化的罕见机会。在这项工作中，聚合物微粒由水杨酸基聚合物（Poly-A）制成，并作为肺部急性炎症的治疗剂进行研究。这种颗粒制剂在将中性粒细胞从肺部转移出去方面表现得非常好，最终减少了基于炎症的损伤。此外，观察到Poly-A颗粒改变中性粒细胞表面炎症分子的表达。
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain problematic due to high mortality rates and lack of effective treatments. Neutrophilic injury contributes to mortality in ALI/ARDS. Here, we developed and evaluated technology for rapid ARDS intervention, where intravenous salicylic acid-based polymer microparticles, i.e., Poly-Aspirin (Poly-A), interfere with neutrophils in blood, reducing lung neutrophil infiltration and injury in vivo in mouse models of ALI/ARDS. Importantly, Poly-A particles reduced multiple inflammatory cytokines in the airway and bacterial load in the bloodstream in a live bacteria lung infection model of ARDS, drastically improving survival. We observed that phagocytosis of the Poly-A microparticles, with salicylic acid in the polymer backbone, altered the neutrophil surface expression of adhesion molecules, potentially contributing to their added therapeutic benefits. Given the proven safety profile of the microparticle degradation products – salicylic acid and adipic acid – we anticipate the Poly-A particles represent a therapeutic strategy in ARDS with a rare opportunity for rapid clinical translation. In this work, polymeric microparticles were fabricated from a salicylate-based polymer (Poly-A) and investigated as a therapeutic for acute inflammation of the lungs. This particle formulation performed exceptionally well in diverting neutrophils away from the lungs, ultimately reducing inflammatory-based damage. Furthermore, Poly-A particles were observed to change the neutrophil surface expression of inflammatory molecules.
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