A “Lung-Trap” Theranostic Strategy for Precision Management of Drug-Resistant Bacterial Pneumonia and Bacteremia

The escalating global crisis of antibiotic resistance demands the development of novel therapeutic strategies. This study proposes a “lung-trap” strategy that shifts the paradigm from systemic chemical eradication to localized physical interception and clearance. An engineered peptide conjugate, namely BTFR, selectively accumulates in the pulmonary vasculature and undergoes self-assembly into bacteria-capturing nanofibers. These nanostructures effectively entrap methicillin-resistant S. aureus (MRSA), prevent its dissemination, and attenuate virulence. The platform further enables real-time NIR-II imaging and exhibits potent photodynamic activity. In vivo studies demonstrated that BTFR efficiently captures bacteria within the lungs, significantly reduces bacterial loading, improves survival rates, and promotes tissue repair in models of MRSA-induced pneumonia and bacteremia. This approach transforms the lung from a passive site of infection into an active defense barrier, offering a promising new paradigm for the treatment of severe bacterial infections.