Gallium phosphate nanoparticles as an antibiotic-free strategy against Pseudomonas aeruginosa lung infections

Rising bacterial resistance and the declining efficacy of existing antibiotics demand new antimicrobial strategies. Gallium ions are analogs of ferric ions and can disrupt bacterial iron homeostasis. However, their effective delivery to infected lungs remains a challenge. Here, we report an antibiotic-free antimicrobial approach utilizing gallium phosphate (GaP) nanoparticles. Flame spray pyrolysis (FSP), an industrially relevant manufacturing process, was employed for the first time to produce GaP nanoparticles with controlled compositions (Ga:P ratios) and average particle sizes ranging from 9 to 23 nm. The GaP nanoparticles displayed potent antibacterial activity against Pseudomonas aeruginosa, a major pathogen in lung infections, by inhibiting both planktonic growth even under iron-rich conditions and biofilm formation. GaP nanoparticles were biocompatible with human lung epithelial cells and caused no histological adverse effects following in vivo pulmonary administration in mice. In a murine lung infection model, intranasal delivery of GaP nanoparticles significantly reduced bacterial burden. This study establishes flame-made GaP nanoparticles as a scalable, antibiotic-free strategy for combating P. aeruginosa lung infections and lays the foundation of flame-made GaP nanoparticles as a new paradigm in precision infection nanomedicine.