Abstract

This nanoplatform achieves targeted delivery to deep-seated abscesses through a neutrophil-hitchhiking strategy. • The platform employs ultrasound-induced ROS and UTMD for synergistic physicochemical eradication of biofilms and bacteria. • Ultrasound-triggered in situ NETs activation enables targeted immune clearance of bacteria without tissue damage. • The platform enables ultrasound visualization for real-time monitoring of disease progression. Bacterial liver abscesses (BLAs), particularly those caused by multidrug-resistant (MDR) bacteria, are difficult to treat effectively with single-modal antibacterial approaches, necessitating the development of combined therapeutic strategies. In this study, we designed an ultrasound-triggered trimodal nanobactericide PLP (PFH@LVFX-PLGA-bPEI, termed PLP). The experimental results demonstrate that PLP nanoparticles are efficiently phagocytosed by neutrophils via complement C3 opsonization and actively transported to deep-seated abscesses through neutrophil chemotaxis. Under low-intensity focused ultrasound (LIFU) irradiation, PLP synergistically delivers trimodal “Physical-Chemical-Immunological” therapy: (1) physically, PLP triggers ultrasound-targeted microbubble destruction (UTMD), generating microjets that physically disrupt biofilm barriers and enhance ultrasound imaging; (2) chemically, PLP enables the site-specific release of LVFX and the generation of reactive oxygen species (ROS) via sonodynamic therapy to kill bacteria; and (3) immunologically, PLP stimulates neutrophils to release neutrophil extracellular traps (NETs) in situ, thereby amplifying local innate immune defenses. This triple strategy achieves precise theranostics for deep-seated abscesses and the eradication of MDR bacteria while effectively avoiding systemic inflammatory responses, providing a novel, precise, safe, and visualizable solution for deep tissue infections.