Inhalable MOF‐Derived Nanoparticles for Sonodynamic Therapy of Bacterial Pneumonia

Abstract 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@TiO 2 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.