CT-sensitized nanoprobe for effective early diagnosis and treatment of pulmonary fibrosis

Early diagnosis is critical for providing a timely window for effective therapy in pulmonary fibrosis (PF); however, achieving this remains a significant challenge. The distinct honeycombing patterns observed in computed tomography (CT) for the primary diagnosis of PF are typically only visible in patients with moderate to severe disease, often leading to missed opportunities for early intervention. In this study, we developed a nanoprobe designed to accumulate at fibroblastic foci and loaded with the CT sensitizer iodide to enable effective early diagnosis of PF. An antibody fragment (Fab') targeting the platelet-derived growth factor receptor-α, which specifically binds to (myo)fibroblasts, was conjugated to the nanoprobe surface to enhance targeting of fibroblastic foci. Additionally, collagenase was employed to facilitate nanoprobe penetration by degrading the local collagen fibers within these foci. This approach led to significant accumulation of the CT sensitizer iodide in fibrotic lung tissues, resulting in enhanced CT imaging for the detection of fibroblastic foci and enabling early diagnosis of PF. Moreover, a dual-drug combination of oltipraz and rosiglitazone was co-loaded into the nanoparticles for the treatment of early-diagnosed PF. Remarkable therapeutic efficacy was observed in model mice with early PF using these nanoparticles. Our findings present a promising strategy for the early diagnosis of PF, potentially offering a valuable time window for effective treatment of this life-threatening disease.