Phage@CeO₂ nanozyme nanoplatform: concurrent bactericidal and detoxifying therapy for sepsis

Sepsis caused by drug-resistant bacteria remains a global health crisis. Under such circumstances, phage therapy represents a promising option. However, phage-mediated bacterial lysis process can release a large amount of lipopolysaccharide (LPS), which in turn triggers inflammatory storms. Herein, we equipped phage with LPS-degrading CeO₂ nanozymes (X03@CeO₂). In vitro, X03@CeO₂ achieved 99.99% bactericidal efficiency against Pseudomonas aeruginosa ( P. aeruginosa ), 63.76% biofilm clearance, and reduced lysis-released LPS to 49.60%. It protected cells from LPS-induced inflammation, as evidenced by the prevention of cell death, normalization of interleukin-6 and tumor necrosis factor-α levels, inhibition of reactive oxygen species production, and blockade of Toll-like receptor 4 activation. In a P. aeruginosa -induced sepsis mouse model, X03@CeO₂ boosted 24-h survival to 87.50%, reduced blood bacterial load and LPS content, and reversed hematological abnormalities and multi-organ damage. X03@CeO₂ not only eradicates pathogens but also degrades leaked virulence factors, thereby mitigating the excessive host immune response. This multimodal strategy presents a promising therapeutic approach for drug-resistant bacterial sepsis.