Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury

作者：Lu Wang, Huasheng Zhang, Liya Sun, Wei Gao, Ye Xiong, Aying Ma, Xiali Liu, Lei Shen, Qiang Li, Hong Yang · 发表于：Journal of Nanobiotechnology · 年份：2020 · DOI：10.1186/s12951-020-00593-7 · 被引用次数：147 · 研究领域：Immune cells in cancer、Nanoplatforms for cancer theranostics、Tissue Engineering and Regenerative Medicine

BACKGROUND: 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. RESULTS: 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. CONCLUSION: This study demonstrated that...