Biosafety assessment of zirconia nanoparticles for drug-resistant chronic bacterial lung infections

Antimicrobial resistance in the treatment of chronic lung infections is the leading cause of morbidity and mortality in patients with diseases such as cystic fibrosis and hospital-acquired lung infections. The present work has been carried out in the Light4Lungs European project, whose aim is the set-up of a new therapeutic scheme, replacing antibiotics with inhalable zirconia nanoparticles (NPs) properly formulated to fight the pathogenic bacteria. To assure the safety of NPs towards human lung cells, we investigated NP biocompatibility/toxicity in normal and tumoral cell lines of the respiratory epithelium. We verified i) the viability of cells incubated for short and long periods with NPs; ii) the cellular uptake of NPs; ii) if NPs are phagocyted by macrophages since the clearance of NPs is of outmost importance to avoid persistent retention of particles in the treated tissues; iv) the genotoxic potential of NPs towards human cells of respiratory tract. Our results show that zirconia NPs are internalized by cells without inducing significant toxic effects against lung cells of the respiratory tract.