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The emergence of multi‐drug resistant (MDR) bacteria poses a serious threat to human health. It has become imperative to develop efficient antimicrobial strategies. Here, a manganese‐doped dopamine‐derived hollow carbon sphere (MnOx/HNCS) is developed as a nanozyme and photothermal agent for the synergistic treatment of MDR bacterial infections. MnOx/HNCS possesses oxidase, superoxide dismutase, and peroxidase like activities and implements self‐cascading enzymatic catalysis to produce superoxide anion (O2•−), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH). Importantly, near‐infrared light facilitates the electron transport of MnOx/HNCS, allowing it to exhibit stable photothermal effects and photo‐enhanced enzymatic activity. Thereby MnOx/HNCS displays a broad‐spectrum synergistic antibacterial efficiency in vitro against six MDR pathogens based on the above photo‐regulated properties. In vivo experiments further demonstrate the excellent antibacterial efficiency of MnOx/HNCS in the MDR bacteria‐infected wound model. Notably, MnOx/HNCS not only has excellent disinfection capacity, but also can accelerate wound healing by stimulating the deposition of the extracellular matrix and reepithelialization. This study proposes a promising antibiotics‐alternative broad‐spectrum antibacterial strategy and paves a new avenue for the establishment of multifunctional photo‐responsive synergistic therapeutic platform. [ABSTRACT FROM AUTHOR]

Clinical therapy of multidrug resistant (MDR) bacteria‐induced deep‐tissue infections such as pneumonia is highly challenging. Ultrasound (US)‐induced sonodynamic therapy (SDT) is a promising strategy for treatment of deep‐tissue diseases given the strong tissue penetration of US. Here, ZIF‐8‐derived carbon@TiO2 nanoparticles (ZTNs) are developed as inhalable sonosensitizers for bacterial pneumonia. ZTNs upon US irradiation exhibit an excellent efficacy to produce reactive oxygen species (ROS) and thereby to kill Gram‐negative MDR bacteria in vitro. Taking advantage of aerosolized intratracheal inoculation, ZTNs can be precisely delivered to lung infection sites, and display an effective SDT‐based elimination of Gram‐negative MDR bacteria in the lung infection models of immunocompetent or immunodeficient mice. Particularly, ZTNs upon US irradiation give a 100% survival rate in the severely immunodeficient NOD/SCID mice with a lethal bacterial pneumonia. In addition, ZTNs have no obvious toxicity at both cellular and animal levels. Metal–organic‐framework‐derived nanoparticles as safe and efficient inhalable sonosensitizer have a great potential to be used for the clinical antibiotics‐alternative treatment of MDR bacterial pneumonia. This study presents a new paradigm for SDT‐based treatment of deep‐tissue bacterial infections, and will expand the nanomedicine application of inorganic sonosensitizers. [ABSTRACT FROM AUTHOR]