Carbon Monoxide-Enhanced antibacterial Therapy: Inhibiting bacterial Self-Perception mechanisms.

The expression of heat shock proteins (HSPs) plays a pivotal role in enhancing bacterial adaptability and repair mechanisms, posing a challenge for effective antibacterial strategies. To address this, we designed multifunctional Au@mSiO2-MnCO/IR780 nanoparticles (NPs) that target key bacterial signaling pathways to suppress HSP expression. Specifically, the system leverages the controlled release of carbon monoxide (CO) to inhibit bacterial perception mechanisms, including the two-component system (TCS), thereby effectively downregulating HSP expression. This inhibition disrupts bacterial adaptability and repair capacity, maintaining the bacteria in a vulnerable state. In this design, Au nanorods serve as highly efficient photothermal agents, while, IR780 generates reactive oxygen species (ROS) and emits fluorescence under near-infrared (NIR) light irradiation. The generated ROS facilitates the release of CO from MnCO, which directly inhibits bacterial TCS and sigma factor system pathway, significantly reducing the expression of bacterial HSPs. Further, Mn2+ catalyzes the decomposition of hydrogen peroxide (H2O2) to produce oxygen (O2), alleviating the oxygen-deficient environment at the abscess site and enhancing PDT efficacy. This innovative approach with TCS inhibition highlights the critical role of CO-mediated signaling pathway disruption in suppressing HSP expression, representing a significant advancement in the field of antibacterial therapy.