A Zinc-Coordinated Glycopolymer for Inhibiting Bacterial Toxins in Management of Acute Pneumonia

Bacterial toxins play a critical role in infections by compromising host defenses, causing host cell death, and inducing excessive immune activation, ultimately leading to severe tissue damage and increased mortality. To combat both the pathogen and its associated toxins, this study developed a bacteria-targeting zinc-coordinated glycopolymer designed to deliver antisense oligonucleotides (ASOs) and absorb lipopolysaccharides (LPS). The functional polymer enhances Pseudomonas aeruginosa internalization efficiency through galactose-mediated bacterial surface interaction. By delivering multiple ASOs, the nanoparticle enables the dual suppression of bacterial growth and quorum sensing, exhibiting potent antibacterial activity. Furthermore, zinc ions coordinated within the glycopolymer impart the ability to bind and adsorb LPS, thereby mitigating the toxin-induced damage to host cells. In a murine model of acute pneumonia, this approach significantly improved survival rates and reduced pro-inflammatory cytokine levels. Consequently, pulmonary inflammation was suppressed, bacterial toxin-induced damage was alleviated, and tissue integrity was preserved. This synergistic strategy of combined sterilization and toxin neutralization offers a novel and synergistic therapeutic approach to combating bacterial infections.