PMID- 32101146 OWN - NLM STAT- MEDLINE DCOM- 20201013 LR - 20201013 IS - 1477-3155 (Electronic) IS - 1477-3155 (Linking) VI - 18 IP - 1 DP - 2020 Feb 26 TI - Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury. PG - 38 LID - 10.1186/s12951-020-00593-7 [doi] LID - 38 AB - 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 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. FAU - Wang, Lu AU - Wang L AD - Department of Pulmonary and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. FAU - Zhang, Huasheng AU - Zhang H AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Sun, Liya AU - Sun L AD - School of Biomedical Engineering, Tianjin Medical University, Tianjin, 300070, China. FAU - Gao, Wei AU - Gao W AD - Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, 200120, China. FAU - Xiong, Ye AU - Xiong Y AD - Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, 200120, China. FAU - Ma, Aying AU - Ma A AD - Department of Pulmonary and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. FAU - Liu, Xiali AU - Liu X AD - Department of Pulmonary and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. FAU - Shen, Lei AU - Shen L AD - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. lshen@shsmu.edu.cn. FAU - Li, Qiang AU - Li Q AD - Department of Pulmonary and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. liqressh@hotmail.com. AD - Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, 200120, China. liqressh@hotmail.com. FAU - Yang, Hong AU - Yang H AD - Department of Pulmonary and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. hongyang@tmu.edu.cn. AD - School of Biomedical Engineering, Tianjin Medical University, Tianjin, 300070, China. hongyang@tmu.edu.cn. LA - eng GR - 81770070/National Natural Science Foundation of China/ GR - 81870064/National Natural Science Foundation of China/ GR - TP2016014/Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning/ GR - 20171923/Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support/ GR - PWYgy2018-06/Outstanding Clinical Discipline Project of Shanghai Pudong/ PT - Journal Article DEP - 20200226 PL - England TA - J Nanobiotechnology JT - Journal of nanobiotechnology JID - 101152208 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Lipopolysaccharides) RN - 130068-27-8 (Interleukin-10) RN - 7440-57-5 (Gold) SB - IM MH - Acute Lung Injury/*drug therapy MH - Animals MH - Anti-Inflammatory Agents/chemistry/pharmacology MH - Bronchoalveolar Lavage Fluid MH - Disease Models, Animal MH - Gold/chemistry/*pharmacology MH - Interleukin-10/metabolism MH - Lipopolysaccharides/pharmacology MH - Lung/drug effects/metabolism MH - Macrophages/*drug effects/metabolism MH - Male MH - Metal Nanoparticles/*chemistry MH - Mice MH - Mice, Inbred C57BL MH - Pneumonia/drug therapy PMC - PMC7045427 OTO - NOTNLM OT - Acute lung injury OT - Alveolar macrophage OT - Gold nanoparticle OT - Inflammation OT - Macrophage polarization OT - Peptide COIS- The authors declare that they have no competing interests. EDAT- 2020/02/27 06:00 MHDA- 2020/10/21 06:00 PMCR- 2020/02/26 CRDT- 2020/02/27 06:00 PHST- 2019/11/23 00:00 [received] PHST- 2020/02/13 00:00 [accepted] PHST- 2020/02/27 06:00 [entrez] PHST- 2020/02/27 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2020/02/26 00:00 [pmc-release] AID - 10.1186/s12951-020-00593-7 [pii] AID - 593 [pii] AID - 10.1186/s12951-020-00593-7 [doi] PST - epublish SO - J Nanobiotechnology. 2020 Feb 26;18(1):38. doi: 10.1186/s12951-020-00593-7.