Intra-tracheal photoacoustic endoscopy in vivo characterizing airway inflammation with a macrophage-targeted contrast-enhanced agent

Airway inflammatory diseases are a major cause of lower respiratory morbidity and impose a substantial socioeconomic burden owing to symptoms such as persistent cough and progressive airway dysfunction. M1-polarized macrophages are key drivers of inflammation in the airway. However, in vivo visualization of them remains challenging. Here, we developed an intra-tracheal photoacoustic endoscopy (IT-PAE) system integrated with a Prussian blue/polyethylenimine@hyaluronic acid (PB/PEI@HA) nanocontrast agent for molecular imaging of airway inflammation. A rabbit model of lipopolysaccharide (LPS)-induced airway inflammation was established, followed by intratracheal administration of PB/PEI@HA. The dynamic distribution of the nanocontrast agent was monitored by IT-PAE. The results demonstrated that PB/PEI@HA selectively accumulated in M1 macrophages within the airway wall. Quantitative analysis revealed that, 24 h after LPS induction, the photoacoustic signal intensity increased by approximately 7-fold and the signal- positive area by approximately 13-fold compared with those of the control group, enabling sensitive detection and assessment of airway inflammation severity. These findings demonstrated that IT-PAE combined with macrophage-targeted molecular contrast imaging, provided a promising strategy for the non-invasive detection of airway inflammatory diseases.