Primary Amine Modified Gold Nanodots Regulate Macrophage Function and Antioxidant Response: Potential Therapeutics Targeting of Nrf2

Int J Nanomedicine. 2020 Oct 29:15:8411-8426. doi: 10.2147/IJN.S268203. eCollection 2020.

Abstract

Background: 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: antioxidant; gold nanodots; inflammation; macrophage.

MeSH terms

  • Amines / chemistry*
  • Antioxidants / metabolism*
  • Cytokines / metabolism
  • Endotoxins / metabolism
  • Gold / chemistry*
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Macrophages / metabolism*
  • Metal Nanoparticles / chemistry*
  • Molecular Targeted Therapy*
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress
  • Phagocytosis
  • Phosphorylation
  • Reactive Oxygen Species / metabolism
  • THP-1 Cells

Substances

  • Amines
  • Antioxidants
  • Cytokines
  • Endotoxins
  • Inflammation Mediators
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Gold
  • Heme Oxygenase-1

Grants and funding

This study was supported by grants MOST-104-2320-B-400-003-MY3 and MOST-108-2320-B-008-001 from the Ministry of Science and Technology in Taiwan, and National Health Research Institutes, Taiwan, ROC (grant number NHRI-108EMPP02).