Biofilm\nMicroenvironment-Mediated Dual-Gases-Driven\nNanomotors for Combating Drug-Resistant Bacterial Infections

Biofilms become increasingly resistant to antibacterial\nagents\nbecause of the presence of extracellular polymeric substances (EPS).\nNanomotors possessing autonomous movement exhibit a high efficacy\nin antibiofilm therapy. Herein, a nanomotor (Cu-tbDMSNs@Arg) driven\nby NO and H<sub>2</sub>S gases is proposed. Cu-tbDMSNs@Arg nanomotors\ncan rapidly penetrate biofilms by releasing NO and H<sub>2</sub>S\nsimultaneously in biofilm microenvironments (BME) with high levels\nof H<sub>2</sub>O<sub>2</sub> and GSH. In addition, the nanomotor\ncontaining Cu<sup>2+</sup> can regulate the Fenton-like reaction to\ngenerate reactive oxygen species (ROS), which substantially enhances\nthe antibacterial effect of the nanomotor, to result in a 2.47 log<sub>10</sub> reduction in bacterial cell counts. Furthermore, in a Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)-infected pyomyositis mice model,\nCu-tbDMSNs@Arg nanomotors can effectively target and accumulate at\nthe site of infection to eliminate biofilm and have anti-inflammatory\nand angiogenic capabilities. This novel BME-mediated NO and H<sub>2</sub>S dual-gas-driven nanomotor offers an appealing alternative\nfor treating biofilm infections with excellent biocompatibility.