Gold nanocluster surface ligand exchange: An oxidative stress amplifier for combating multidrug resistance bacterial infection.

The bacteria redox balance between oxidizing and reducing species plays a critical role in bacterial activities, and the disruption of this homeostasis offers a flexible antibacterial strategy to combat bacterial multidrug resistance. Here, the ligand exchange strategy of Au NCs was first developed to construct an oxidative stress amplifier. We cleverly utilized the reactive oxygen species (ROS) generation ability of histidine (His)-stabilized Au NCs. Cinnamaldehyde (CA) was modified on the surface of Au NCs through an aldimine condensation reaction, and the modification of CA on the surface of Au NCs further accelerated ROS generation. Meanwhile, the strong Au-S interaction between CA-Au NCs and thiols facilitated the ligand exchange of surface histidine-cinnamaldehyde (His-CA) with thiol molecules, causing the consumption of thiols in bacteria and the release of His-CA, which thus finally resulted in efficient bacterial cell death. CA-Au NCs showed excellent antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA), including 48-h biofilm removal and the treatment of a pig skin wound infection model, representing a promising antibacterial agent for clinical applications.