Department of Pulmonary and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
J Nanobiotechnology. 2020 Feb 26;18(1):38. doi: 10.1186/s12951-020-00593-7.
Macrophage polarization and reprogramming in the lung play a critical role in the initiation, development and progression of acute lung injury (ALI). Regulating the activation and differentiation of pulmonary macrophages may provide a potential therapeutic strategy to treat ALI. We previously developed a novel class of anti-inflammatory nanoparticles (P12) that can potently inhibit Toll-like receptor (TLR) signaling in macrophages. These bioactive nanodevices were made of gold nanoparticles (GNPs) coated with hexapeptides to not only ensure their physiological stability but also enable GNPs with TLR inhibitory activity.
In this study, using a lipopolysaccharide (LPS) induced ALI mouse model, we showed that P12 was able to alleviate lung inflammation and damage through reducing the infiltration of inflammatory cells and increasing the anti-inflammatory cytokine (IL-10) in the lung. These results prompted us to investigate possible macrophage polarization by P12. We first confirmed that P12 primarily targeted macrophages in the lung to exert anti-inflammatory activity. We then showed that P12 could drive the polarization of mouse bone marrow-derived macrophages (BMDMs) toward anti-inflammatory M2 phenotype. Interestingly, in the ALI mouse model, P12 was able to increase the alveolar M2 macrophages and reduce both the alveolar and interstitial M1 macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues.
This study demonstrated that peptide-coated GNPs could induce M2 macrophage polarization in vitro and in vivo to effectively regulate lung inflammation, protect lung from injuries and promote inflammation resolution. The ability of regulating macrophage polarization together with TLR inhibition made such a bioactive nanodevice a new generation of potent therapeutics to treat ALI.
肺中巨噬细胞的极化和重编程在急性肺损伤（ALI）的发生、发展和进展中起着关键作用。调节肺巨噬细胞的激活和分化可能为治疗 ALI 提供一种潜在的治疗策略。我们之前开发了一类新型抗炎纳米粒子（P12），能够强烈抑制巨噬细胞中的 Toll 样受体（TLR）信号。这些生物活性纳米器件由金纳米粒子（GNPs）制成，表面覆盖六肽，不仅确保其生理稳定性，而且使具有 TLR 抑制活性的 GNPs 得以实现。
在这项研究中，我们使用脂多糖（LPS）诱导的 ALI 小鼠模型表明，P12 通过减少炎症细胞浸润和增加肺部抗炎细胞因子（IL-10）来减轻肺部炎症和损伤。这些结果促使我们研究 P12 可能的巨噬细胞极化。我们首先证实 P12 主要靶向肺部巨噬细胞发挥抗炎作用。然后我们表明 P12 可以驱动小鼠骨髓来源的巨噬细胞（BMDMs）向抗炎 M2 表型极化。有趣的是，在 ALI 小鼠模型中，P12 能够增加肺泡 M2 巨噬细胞，并减少支气管肺泡灌洗液（BALF）和肺组织中肺泡和间质 M1 巨噬细胞。
这项研究表明，肽涂层的 GNPs 可以在体外和体内诱导 M2 巨噬细胞极化，有效调节肺部炎症，保护肺部免受损伤，并促进炎症消退。这种生物活性纳米器件抑制 TLR 并调节巨噬细胞极化的能力使其成为治疗 ALI 的新一代有效治疗方法。
