Early diagnosis of fibrogenic remodeling in idiopathic pulmonary fibrosis by targeting matrix metalloproteinase-2 with CT imaging

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited treatment options and a poor prognosis, underscoring the critical need for early diagnosis. Conventional methods like high-resolution computed tomography (HRCT) and lung biopsy often fail to detect fibrogenic remodeling in its initial stages. To address this challenge, we developed a novel, non-invasive CT imaging nanoprobe for the early diagnosis of IPF. This probe, termed MSNPs, consists of gold nanoparticles functionalized with MMP2-cleavable peptides. In vitro, MSNPs demonstrated high sensitivity and specificity for MMP2, showing significant intracellular accumulation upon activation. In a bleomycin-induced mouse model of IPF, CT imaging with MSNPs revealed a substantial increase in signal intensity at lesion sites as early as days 5 and 10 post-induction. This increase correlated with fibrosis severity, as confirmed by histopathology, elevated MMP2 expression, and measured nanoprobe accumulation in lung tissues. Collectively, this MMP2-targeted CT imaging strategy represents a promising non-invasive method for the detection of fibrogenic remodeling in IPF.