A Drug-Repurposing Nanotheranostic for Synergistic Management of Resistant Bacterial Pneumonia

The rising threat of antibiotic resistance severely compromises the treatment of bacterial pneumonia, underscoring the urgent need for innovative and comprehensive therapeutic strategies. Here, we developed an innovative theranostic nanoplatform (Dex/BTGd) through the coordinated assembly of tetracycline, gadolinium ion (Gd 3+ ) and baicalin (Ba), which acts synergistically to combat infection, enable non-invasive magnetic resonance imaging (MRI), and regulate the lung microenvironment. Dex/BTGd demonstrated potent antibacterial activity against clinically relevant pathogens, effectively disrupting biofilms and overcoming tetracycline resistance. The incorporated Gd 3+ allowed targeted visualization of pulmonary infection sites by MRI, facilitating timely disease assessment. Beyond its direct antibacterial effects, the nanoplatform modulated the inflammatory microenvironment by scavenging reactive oxygen species, promoting macrophage polarization from the pro-inflammatory to the anti-inflammatory phenotype, and suppressing profibrotic transforming growth factor-β signaling. In a murine model of tetracycline-resistant Pseudomonas aeruginosa pneumonia, Dex/BTGd significantly reduced bacterial load, alleviated pulmonary edema and fibrosis, and enabled targeted MRI visualization of infected lesions. This integrated strategy of pathogen clearance, microenvironment modulation, and tissue repair offers a multifaceted solution to drug-resistant bacterial pneumonia, providing a promising blueprint for next-generation anti-infective systems.