An inhalable nanoparticle enabling virulence factor elimination and antibiotics delivery for pneumococcal pneumonia therapy

Streptococcus pneumoniae (S. pneumoniae) is a major cause of community-acquired pneumonia. Current standard clinical therapies mainly focus on combating S. pneumoniae through Antibiotics. However, the limited delivery of Antibiotics and the undetoxified hydrogen peroxide (H₂O₂) virulence factor secreted by S. pneumoniae impede the therapeutic outcomes. Here we report an inhalable catalase (CAT)-tannic acid (TA) nanoassembly for local Antibiotic (levofloxacin) delivery and simultaneously neutralizing the secreted H₂O₂ virulence factors to treat pneumococcal pneumonia. After aerosol inhalation, the inhalable formulation (denoted as CT@LVX) effectively accumulates in lung tissues through TA-mediated mucoadhesion. CAT can reduce alveolar epithelial cells Apoptosis by catalyzing the decomposition of accumulated H₂O₂ in the infected lung tissues. In synergy with Antibiotic LVX-mediated S. pneumoniae elimination, CT@LVX significantly decreases lung injury companied with reduced inflammatory, resulting in 100 % survival of mice with pneumonia. In a clinically isolated S. pneumoniae strain-induced pneumonia mouse model, CT@LVX also shows superior outcomes compared to the traditional Antibiotic treatment, highlighting its potential clinical application prospects.

Aerosol inhalation; Antibiotics delivery; Hydrogen peroxide; Pneumococcal pneumonia.