Gold Nanoclusters Exert Bactericidal Activity and Enhance Phagocytosis of Macrophage Mediated Killing of Fusobacterium nucleatum

Abstract

Fusobacterium nucleatum is a typical periodontal opportunistic pathogen that contributes to inflammatory diseases at oral or extra-oral sites. The emergence of antibiotics resistance calls for a substitute therapeutic strategy to control bacterial infections effectively. In addition, macrophage is an essential part of host defense against microorganism invasion in vivo. Herein, we synthesized gold nanoclusters (AuNCs) as potent antibacterial material to kill F. nucleatum through bactericidal behavior and pro-phagocytic activity. Firstly, we evaluated the bactericidal effect of AuNCs on F. nucleatum by the means of plate counting, growth curve measurement, bacterial viability analysis, and live/dead fluorescent imaging. Morphological changes and the intracellular reactive oxygen species levels of bacteria were further analyzed to explore the possible mechanisms. Additionally, the impact of AuNCs on the ability of macrophages to uptake bacteria under normal and inflammatory circumstance was also evaluated by fluorescent imaging. We found that AuNCs exhibited superior antibacterial performance on F. nucleatum in vitro by a combination of membrane disruption and oxidative stress. Furthermore, in the presence of AuNCs, macrophages displayed enhanced phagocytosis against F. nucleatum without inducing any significant cytotoxicity. Therefore, AuNCs are providing a new platform for the prevention and treatment of F. nucleatum-associated diseases.

Antibiofilm activity of ultra-small gold nanoclusters against Fusobacterium nucleatum in dental plaque biofilms

“…6-mercaptohexanoic acid (MHA)-protected AuNCs were synthesized by one-pot reduction of sodium borohydride (NaBH 4 ), as described in previous studies [ 27 , 30 ]. The structure of AuNCs were characterized using a Lambda 25 UV/Vis Spectrophotometer (PerkinElmer, Waltham, MA, USA) and Nicolet iS500 Fourier Transform Infrared (FTIR) Spectrometer (Thermo Fisher Scientific, Waltham, MA, USA).…”

A new direction in periodontitis treatment: biomaterial-mediated macrophage immunotherapy

“…The regulation of macrophage antimicrobial capabilities primarily involves the modulation of reactive oxygen species (ROS) and the modulation of phagocytic activity. In a study, Chen et al [ 154 ] created gold nanoclusters (AuNCs) as antibacterial materials for the treatment of periodontitis. The findings demonstrated that AuNCs boosted the antibacterial impact against Fusarium in vitro by inducing excessive ROS generation, and that AuNCs promote the phagocytosis of macrophages to F. nuclearum.…”

Recent advancements in design of nucleic acid nanocarriers for controlled drug delivery

“…[4][5][6] Most affected has been cancer treatment due to the development of a variety therapeutic agents designed with molecular precision for the treatment of specific cancer genotypes. 7 Additionally, advances in diagnostics and treatment of, e.g., reproductive diseases, 8 Alzheimer's, 9 infectious disease, 10 cardiovascular disease, 11 viral diseases, 12 chronic inflammation, 13 and neurodegenerative diseases 14 have showcased the utility of nanomedicine in a broad range of diseases. At its core the advantage of nanomedicine lies in the tunability of nanomaterials which allow for highly versatile and multifunctional therapeutic agents, often referred to as personalized medicines (Fig.…”