Inhalable MOF-Derived Nanoparticles for Sonodynamic Therapy of Bacterial Pneumonia

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.