Recent advances in gold and zinc oxide nanoparticles: Antibiofilm action, mechanisms beyond ROS generation, and in vivo efficacy.

Gold (Au) and zinc oxide (ZnO) nanoparticles (AuNPs/ZnONPs, respectively) are well-established antimicrobial nanomaterials with broad-spectrum activity and multifaceted mechanisms of action. This review highlights recent advances, focusing on their antibiofilm activity, novel antimicrobial mechanisms, and therapeutic potential in in vivo infection models. Beyond traditional antibacterial effects, these nanoparticles exhibit potent antibiofilm activity and disrupt multiple cellular targets, including cell wall biosynthesis, membrane transport and efflux pumps, energy metabolism, biofilm formation, quorum sensing pathways, and DNA replication and repair, thereby targeting microorganisms on several fronts simultaneously. In vivo studies, particularly biofilm-relevant infection models, remain comparatively limited; however, available evidence indicates that AuNPs/ZnONPs can reduce bacterial burden, promote wound healing, and improve survival, positioning them as promising candidates for next-generation therapeutics. However, despite promising outcomes, challenges such as nanoparticle cytotoxicity, stability, and delivery efficiency remain significant hurdles to clinical translation. Careful optimization of nanoparticle physicochemical properties, along with the development of advanced functionalization and targeting strategies, will be crucial for enhancing the therapeutic index and safety. Moreover, combining these nanoparticles with existing antibiotics and leveraging computational tools, including artificial intelligence, could accelerate the design of next-generation nanotherapeutics.