Enhanced Antimicrobial Efficiency of Gold Nanoclusters via Improved Sonodynamic Activity and Out-Membrane Crossing Capacity

Antimicrobial sonodynamic therapy (SDT) holds great promise in clinical practice regarding its noninvasiveness, high safety profile, and absence of resistance concern. However, exploring high-efficiency sonodynamic sensitizers is slow-moving and remains a big challenge. We, herein, employed gold nanoclusters (Au NCs) as a novel class of sonodynamic sensitizers, demonstrating notable antimicrobial efficacy in treating infected wounds. Specifically, l-arginine (Arg) and 6-azido-2-thiothymidine (ATT) cocapped Au NCs featured enhanced structural rigidity, suppressing nonradiative relaxation of excited electrons and achieving a reactive oxygen species (ROS) yield exceeding 45%. Moreover, the modification of ATT-Au NCs by Arg imparted amino acid-like properties to the Au NCs, while the ultrasound (US) up-regulates the expression of OmpF porins in E. coli. This synergy resulted in a burst of ROS production within the bacterial cells, ultimately leading to a four-order-of-magnitude reduction in microbial viability.