Bio-Mimicking Nanoparticle System Facilitates Sonodynamic-Mediated Clearance of Extensively Drug-Resistant Bacteria.

The increasing prevalence of carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii (XDR-Ab) poses a critical challenge in treating hospital-acquired pulmonary infections. In this study, we developed a biomimetic neutrophil membrane-coated nanoparticle system, NM@PCN-TIG, for the targeted delivery of tigecycline (TIG). The system utilizes the porphyrin-based metal-organic framework (MOF) PCN-224 as the core of the nanoparticle, encapsulating TIG and coated with a neutrophil membrane (NM) to enhance immune evasion and targeting of infection sites. Its loading efficiency, controlled release properties, cytotoxicity, and bactericidal activity under ultrasound mediation were systematically evaluated in vitro and in vivo. Our results demonstrated that NM@PCN-TIG significantly enhanced the bactericidal efficacy of TIG, increased reactive oxygen species (ROS) production, and promoted macrophage polarization toward an anti-inflammatory phenotype. This innovative biomimetic TIG nanosystem shows great potential as a platform for addressing XDR-Ab-induced pneumonia.