Bacterial infections have caused serious threats to public health due to the antimicrobial resistance in bacteria. Recently, gold nanoclusters (AuNCs) have been extensively investigated for biomedical applications because of their superior structural and optical properties. Great efforts have demonstrated that AuNCs conjugated with various surface ligands are promising antimicrobial agents owing to their high biocompatibility, polyvalent effect, easy modification and photothermal stability. In this review, we have highlighted the recent achievements for the utilizations of AuNCs as the antimicrobial agents. We have classified the antimicrobial AuNCs by their surface ligands including small molecules (<900 Daltons) and macromolecules (>900 Daltons). Moreover, the antimicrobial activities and mechanisms of AuNCs have been introduced into two main categories of small molecules and macromolecules, respectively. In accordance with the advancements of antimicrobial AuNCs, we further provided conclusions of current challenges and recommendations of future perspectives of antimicrobial AuNCs for fundamental researches and clinical applications.

Elucidating the metabolic mechanism of gold nanoclusters (AuNCs) in bacteria will play a pivotal role in bacterial detection and inhibition. A facile method to investigate the metabolic mechanism of AuNCs is demonstrated in this work. The cysteine-conjugated gold nanoclusters (Cys-AuNCs) were successfully prepared with orange-red fluorescence, high water solubility, and superior biocompatibility by one-pot green synthesis to determine bacterial metabolism. The suggested metabolic process was that Cys-AuNCs were metabolized by Escherichia coli, as verified through a decrease in the fluorescence intensity that was clearly detected at 30 min, indicating the breakage of cysteine on Cys-AuNCs, which was further confirmed via X-ray photoelectron spectroscopy (XPS) that was used to observe the decrease in the size of Cys-AuNCs after being metabolized. The metabolic kinetics of Cys-AuNCs was determined by fitting the change in the fluorescence of Cys-AuNCs as a function of incubation time with E. coli, in which the rate constant could be a useful indicator for detecting different bacteria. In addition, the death of E. coli was characterized by an increase in intracellular reactive oxygen species (ROS) through metabolism. After the metabolism of cysteine on Cys-AuNCs by E. coli, significant intracellular ROS generation was induced by the AuNCs that killed the bacterium due to its lack of the ROS scavenger, cysteine. Our work provides a potential rapid method for bacterial detection and inhibition.

As bacterial resistance is becoming increasingly serious, the development of antibacterial nanomaterials is an effective method of solving this problem. Gold nanoparticles have good stability and excellent biocompatibility and are easily modified, and their antibacterial properties can be enhanced by changing their structure and size or adding ingredients. Gold nanoparticles are also excellent drug carriers that can improve the antibacterial effects of loaded antibacterial drugs. After being modified and combined with other antibacterial drugs, gold nanoparticles can also play a better antibacterial role for effective antibacterial strategies against some resistant bacteria. Gold nanoparticles have photothermal effects, and modified gold nanoparticles can be a good medium for photothermal treatments to kill bacteria. By adding functionally modified gold nanoparticles, many materials can obtain much needed antibacterial properties. Gold nanoparticles can also be combined with cations, low-temperature plasma, various surface ligands, and other potential antibacterial agents. In short, the antibacterial characteristics of functionalized gold nanoparticles demonstrate that they have considerable practical application value and provide more ideas to solve antibacterial problems. At the same time, the application of gold nanoparticles in oral biology is also increasing.