Bioinspired Sonodynamic Nano Spray Accelerates Infected Wound Healing via Targeting and Disturbing Bacterial Metabolism

Abstract Bacterial infections pose a major concern for the medical community, especially regarding wound healing. Traditional passive antibiotic therapies can be cytotoxic and lead to bacterial resistance, posing a continuing challenge to treat. Based on precision therapy, a novel targeted‐delivery nanosystem is developed to efficiently eliminate bacteria and promote bacteria‐infected wound healing. Macrophage membranes pre‐activated by Staphylococcus aureus (MM_Sa) are prepared. In doing so, Toll‐like receptors (TLRs), a typical pathogen‐associated molecular pattern (PAMP), are significantly higher than normal macrophage membranes (MM₀). Subsequently, MM_Sa are coated onto ultrasound‐triggered piezocatalytic nano‐barium titanate (BaTiO₃, BTO) surfaces, and these two components are assembled to form a novel targeting delivery nanosystem, namely BTO@MM_Sa. The in vitro and in vivo results demonstrate that the biocompatible BTO@MM_Sa nanosystem can target infected areas and rapidly generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) irradiation, as well as accelerate wound healing. Furthermore, prokaryotic RNA‐seq transcriptomics reveals that changes in bacterial membrane function and substance, and energy metabolism are responsible for the targeted antibacterial ability of BTO@MM_Sa with US. Compared to widely reported unselective antibacterial agents, this novel targeted delivery nanosystem has potential for precise bacterial infection treatment by using macrophage membrane functions.