Gallium-Carbenicillin Framework Coated Defect-Rich Hollow TiO2as a Photocatalyzed Oxidative Stress Amplifier against Complex Infections

Development of new strategies with high antimicrobial capability against complex bacterial infections is still challenging. Herein, a three-in-one synergistic antimicrobial platform is presented based on gallium-carbenicillin framework coated defect-rich hollow TiO(2)nanoshells (H-TiO2-x@MOF), for simultaneous eradicating methicillin-resistantStaphylococcus aureus(MRSA) andPseudomonas aeruginosa(PA) in complex infections, which are the two most common bacteria in wounds. The metal gallium can disrupt bacterial antioxidation system using a Trojan horse strategy by substituting iron in the antioxidant enzymes, and finally increase bacterial susceptibility to oxidants. Meanwhile, oxygen-deficient hollow TiO(2-)(x)nanoshells (H-TiO(2-)(x)NSs) can efficiently bind to the bacteria and promote local generation of abundant reactive oxygen species (ROS) under visible-light irradiation. Thus, the combination of gallium (antioxidant enzyme inhibitor) and black H-TiO(2-)(x)NSs (ROS generator) constitutes a photocatalyzed oxidative stress amplifier that can boost ROS accumulation to destroy pathogens thoroughly. In addition, carbenicillin (Car), as the organic ligand coordinated to gallium ion, also acts as a broad-spectrum antibacterial agent against PA and shares the responsibility for combating complex infections simultaneously. In view of the superior antibacterial ability, accelerated healing of infected wounds, and good biosafety, the H-TiO2-x@MOF potentially provides an alternative antibacterial agent to combat complex bacterial infections.