Endotoxin‐Capturing Nitric Oxide‐Releasing Nanoproducers Synergistically Integrated with Photodynamic Therapy for Bacterial Biofilm Infections

Abstract The challenge of multispecies bacterial biofilms involves secondary infections from biofilm dispersion while failing to clear resident‐bacteria, along with health risks from endotoxins. Although photodynamic therapy simultaneously eliminates biofilms and resident‐bacteria, its effectiveness is limited by the short half‐life of reactive oxygen species (ROS). And the slightly acidic properties of biofilms offer opportunities to mitigate anionic endotoxin hazards. Consequently, a nanoproducer is developed that releases nitric oxide by leveraging its prolonged half‐life and interaction with superoxide anions to extend the range of ROS oxidation. Meanwhile, the nanoproducer can respond to the biofilm's pH, gaining a strong positive charge to effectively capture released endotoxin during treatment. This research indicates that nanoproducers effectively disperse biofilms and improve their penetration into polymeric substances, leading to efficient reduction of bacterial burden in mice harboring biofilm and abscess models. Additionally, nanoproducers effectively reduce inflammatory cytokine levels and immune cell infiltration caused by endotoxin. The nanoplatform, therefore, demonstrates remarkable promise in combating bacterial biofilm infections and alleviating the risks associated with endotoxins.