Phenylboronic Acid-Modified Copper Nanozymes as Nanoscavengers of Bacterial Polysaccharides Causing Acute Lung Injury.

Abstract

Acute lung injury (ALI), especially burn-induced cases complicated by secondary infections and hyperinflammation, remains challenging to treat. This study developed 4-mercaptobenzoic acid (MPBA)-modified copper nanozymes (CuMPBA) to simultaneously combat bacterial infections and toxin-triggered immune overactivation. CuMPBA binds bacterial surface polysaccharides via boronate ester bonds, neutralizing lipopolysaccharides (LPS) and lipoteichoic acid (LTA). It demonstrates dual enzymatic activity: peroxidase (POD)-like and glutathione peroxidase (GPx)-like activities for antimicrobial effects. Additionally, CuMPBA disrupts Streptococcus pneumoniae (Sp) metabolism by interfering with thiamine utilization, amino acid synthesis, DNA processes, and energy production. In burn-ALI mice with secondary pneumonia, CuMPBA restored lung architecture, suppress TNF-α/IL-1β/IL-6 levels, and modulated inflammatory pathways by activating Nrf2 while inhibiting NF-κB. These synergistic mechanisms (precise bactericidal action combined with toxin neutralization) establish CuMPBA as a promising dual-target therapeutic strategy for complex burn-associated ALI. The multifunctionality of nanozymes addresses both infection control and inflammation resolution, offering new potential for managing this severe pathological condition.