Biofilm Microenvironment-Mediated Dual-Gases-Driven Nanomotors for Combating Drug-Resistant Bacterial Infections

Biofilms become increasingly resistant to antibacterial agents because of the presence of extracellular polymeric substances (EPS). Nanomotors possessing autonomous movement exhibit a high efficacy in antibiofilm therapy. Herein, a nanomotor (Cu-tbDMSNs@Arg) driven by NO and H2S gases is proposed. Cu-tbDMSNs@Arg nanomotors can rapidly penetrate biofilms by releasing NO and H2S simultaneously in biofilm microenvironments (BME) with high levels of H2O2 and GSH. In addition, the nanomotor containing Cu2+ can regulate the Fenton-like reaction to generate reactive oxygen species (ROS), which substantially enhances the antibacterial effect of the nanomotor, to result in a 2.47 log10 reduction in bacterial cell counts. Furthermore, in a Methicillin-resistant Staphylococcus aureus (MRSA)-infected pyomyositis mice model, Cu-tbDMSNs@Arg nanomotors can effectively target and accumulate at the site of infection to eliminate biofilm and have anti-inflammatory and angiogenic capabilities. This novel BME-mediated NO and H2S dual-gas-driven nanomotor offers an appealing alternative for treating biofilm infections with excellent biocompatibility.