Gold nanoclusters treat intracellular bacterial infections: Eliminating phagocytic pathogens and regulating cellular immune response

Intracellular bacterial infection is underlying many serious human disorders, leading to high morbidity and mortality. The development of safe and efficient therapeutic agents is the most effective solutions to combat intracellular bacterial infections. Recently, ultrasmall gold nanoclusters (AuNCs) have emerged as an innovative nanoantibiotics against multidrug-resistant bacterial infections due to their inherent antibacterial activity. However, the therapeutic effects of AuNCs on intracellular bacterial infections and their effects on host cells still remain unvisited. Here, we demonstrate the therapeutic potential of 4,6-diamino-2-mercaptopyrimidine-functionalized AuNCs (AuDAMP) for intracellular multidrug-resistant infections in a co-culture model of macrophages and methicillin-resistant Staphylococcus aureus (MRSA). The AuNCs were found to show a superior intracellular antibacterial capability, which can eliminate most of the MRSA phagocytosed by macrophages, and without exhibiting obvious cytotoxicity on host RAW 264.7 macrophages at tested concentrations. More importantly, treatment of AuDAMP exerts critical roles on enhancing the innate immune response to defend against pathogens invading inside the host cells and alleviating the bacterial infection-induced inflammatory response to avoid pyroptosis by up-regulating significantly xenophagy level in macrophages. Taken together, our results suggest that AuNCs hold great potential for the treatment of intracellular bacterial infections.