Inhalable polarization enhanced nanocatalysts for piezoelectric sonodynamic therapy of lethal bacterial pneumonia.

Abstract

Multidrug-resistant (MDR) bacterial pneumonia poses significant therapeutic challenges due to deep tissue localization and limited antibiotic efficacy. Here, we present an inhalable piezoelectric nanocatalyst (poled potassium bismuth titanate, PKBTO) that enables potent, non-antibiotic sonodynamic therapy. Leveraging robust ferroelectric polarization, PKBTO exhibit a markedly enhanced piezoelectric response, promoting efficient charge separation and reactive oxygen species (ROS) generation under clinically relevant ultrasound stimulation. Compared with nonpolarized piezoelectric nanocatalysts, PKBTO achieve a 260.2% increase in ROS yield and a >95% bactericidal efficiency against MDR P. aeruginosa in vitro. In a lethal mouse pneumonia model, aerosolized treatment reduced pulmonary bacterial burden by around 92%, restored lung architecture, normalized inflammatory markers, and improved survival rates to 70% without systemic toxicity. This work demonstrates that ferroelectric polarization engineering provides a powerful route to enhance piezoelectric nanocatalyst performance, offering a safe and effective inhalable sonodynamic platform for deep-seated respiratory infections that are refractory to conventional antibiotics.