International Journal of Nanomedicine (Oct 2020)
Primary Amine Modified Gold Nanodots Regulate Macrophage Function and Antioxidant Response: Potential Therapeutics Targeting of Nrf2
Abstract
Yueh-Hsia Luo,1 Hsien-Jen Cheng,2 Feng-Yuan Tsai,2 Tsui-Chun Tsou,2 Shu-Yi Lin,3 Pinpin Lin2 1Department of Life Sciences, National Central University, Taoyuan City 32001, Taiwan; 2National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County 35053, TaiwanCorrespondence: Yueh-Hsia LuoDepartment of Life Sciences, National Central University, No. 300, Zhongda Road, Zhongli District, Taoyuan City 32001, TaiwanTel +886-34227151Fax +886-34228482Email [email protected] LinNational Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, TaiwanTel +886-37246166Fax +886-37587406Email [email protected]: Gold nanoparticles with high biocompatibility and immunomodulatory properties have potential applications in the development of new diagnostic and therapeutic strategies for nanomedicine. Nanoparticles targeting macrophages can manipulate or control immunological diseases. This study assessed the activity of dendrimer-encapsulated gold nanodots (AuNDs) with three surface modifications [ie, outfacing groups with primary amine (AuNDs-NH2), hydroxyl (AuNDs-OH), and quaternary ammonium ions (AuNDs-CH3)] regulated macrophage function and antioxidant response through Nrf2-dependent pathway.Methods: AuNDs were prepared and characterized. Intracellular distribution of AuNDs in human macrophages was observed through confocal microscopy. The activity of AuNDs was evaluated using macrophage functions and antioxidant response in the human macrophage cell line THP-1.Results: AuNDs-NH2 and AuNDs-CH3, but not AuNDs-OH, drove the obvious Nrf2-antioxidant response element pathway in THP-1 cells. Of the three, AuNDs-NH2 considerably increased mRNA levels and antioxidant activities of heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 in THP-1 cells. IL-6 mRNA and protein expression was mediated through Nrf2 activation in AuNDs-NH2-treated macrophages. Furthermore, Nrf2 activation by AuNDs-NH2 increased the phagocytic ability of THP-1 macrophages.Conclusion: AuNDs-NH2 had immunomodulatory activities in macrophages. The findings of the present work suggested that AuNDs have potential effects against chronic inflammatory diseases via the Nrf2 pathway.Keywords: gold nanodots, macrophage, antioxidant, inflammation
