Development of cysteine-sensitive bimodal probes for <i>in situ</i> monitoring of early-stage pulmonary fibrosis progression and therapeutic effects

Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by excessive extracellular matrix deposition and lung scarring, leading to impaired lung function, severe respiratory distress, and potentially fatal outcomes. Early diagnosis of PF is crucial for optimizing treatment strategies to improve patient prognosis. However, an activated near-infrared fluorescent (NIRF) and photoacoustic (PA) bimodal probe for non-invasive <i>in situ</i> imaging of PF is still lacking. In this study, we developed a novel cysteine-sensitive NIRF/PA dual-modal probe, MR-Cys, for <i>in situ</i> monitoring of early progression and the therapeutic response in a mouse model of PF. The probe MR-Cys selectively detects cysteine (Cys) levels <i>in vivo</i>, thereby activating both NIRF and PA signals. Using NIRF/PA dual-modal imaging technology, MR-Cys successfully tracked fluctuations in Cys levels within the PF mouse model. After treatment with nintedanib (OFEV), a notable decrease in both PA and NIRF signal intensities was observed in the treated mice, indicating that MR-Cys can be used to assess the therapeutic efficacy for PF. Therefore, MR-Cys not only holds great promise for early detection of pulmonary fibrosis progression, but also offers a precise monitoring tool for the optimization of personalized treatment plans.