Laser–Ultrasound Responsive Nanoreactor to Remodel the Microenvironment of Antibiotic-Resistant Bacterial Infection for Diabetic Wound Healing

Diabetic wounds with drug-resistant bacterial infections pose a formidable clinical challenge, which is attributed to adverse microenvironments, including hypoxia, biofilm formation, and insufficient reactive oxygen/nitrogen species (ROS/RNS). To overcome these issues, a laser-ultrasound responsive nanoreactor that comprises NO₂^--intercalated and defect-rich CoMn-layered double hydroxide (LDH) on black phosphorus (BP) nanosheets (D-CoMn LDH-NO₂@BP) is fabricated. It exhibits catalase-like activity for O₂ generation, facilitates NO release under acidic conditions, and promotes ROS/RNS generation upon laser-ultrasound activation, resulting in ferroptosis, biofilm degradation, and hypoxia alleviation for accelerated wound healing. The enhanced ROS generation is caused by the increased Co²⁺ state and strong electronic polarization at the LDH/BP interface. <i>In vitro</i> testing shows that the antibacterial efficacy is 3.3- and 2.6-fold that of pristine LDH for two drug-resistant bacteria. <i>In vivo</i> experiments present a 3.2-fold wound-healing rate over that of pristine LDH, presenting a laser-ultrasound remodeled microenvironment strategy for diabetic wound healing.