Engineering of polymers decorated bimetallic nanoparticles improves bacterial cuproptosis death in acute lung injury and pediatric severe pneumonia

Abstract

Pediatric severe pneumonia represents a significant global infectious illness, characterized by elevated morbidity and mortality rates. In light of antibiotic misuse and bacterial biofilm resistance, various metal-based compounds have been established. Nevertheless, the elevated oxygen levels in the lungs enable certain aerobic pathogenic bacteria to exhibit significant tolerance to oxygen and reactive oxygen species (ROS), rendering metal-based materials reliant on ROS potentially ineffective in therapeutic applications. Motivated by the susceptibility to cuproptosis in aerobic respiratory cells, we developed an antibacterial copper nanocomposite. We demonstrated that it can efficiently induce cuproptosis-like mortality in the lungs of aerobic bacteria. To overcome the challenges of in vivo cuproptosis, manganese dioxide was initially used to reduce protective glutathione, which binds copper and thereby prevents its interaction with proteins, thereby facilitating antibacterial action through immunological improvement. Cuproptosis-like cell death necessitates a substantial quantity of copper ions. To satisfy this demand, we provide positively hydrophilic altered CM nanoparticles that efficiently traverse the lung mucus layer via local administration, with copper ions subsequently released rapidly by the acidic conditions at the infection site, thereby enhancing the destruction of bacterial biofilms in conjunction with manganese. This drug-delivery method can efficiently address pediatric severe pneumonia, while mitigating systemic toxicity associated with high dosages of copper.