An allysine-reactive NIR probe with spatiotemporal precision for early diagnosis and imaging-guided therapy of idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease marked by dysregulated extracellular matrix remodeling and oxidative stress. Current challenges in IPF management include the lack of precise tools for early diagnosis, dynamic monitoring of fibrosis progression, and real-time therapeutic evaluation. However, developing a versatile material with integrated diagnosis and precision treatment tracking for IPF remains a great challenge. Given that hypochlorous acid (HOCl) plays a crucial oxidative role in IPF, we report an allysine-reactive near-infrared (NIR) fluorescent probe (MBT), which leverages covalent bonding between its amino group and aldehyde allysine (a fibrosis biomarker) to achieve spatiotemporally resolved targeting of fibrotic lesions. This strategy enables HOCl-activated NIR imaging with high specificity and sensitivity, facilitating real-time tracking of oxidative stress dynamics in IPF. Using MBT, we dynamically mapped stage-dependent HOCl fluctuations in IPF mice and established a robust correlation between fluorescence signals and fibrotic severity, underscoring its potential for early diagnosis of IPF. Furthermore, MBT served as an imaging-guided precision therapeutic platform, revealing the dual attenuation of HOCl-driven oxidative injury and fibrosis during astaxanthin (AST) treatment. Mechanistic studies demonstrated that AST alleviated HOCl-mediated pathology by modulating the Nrf2/HO-1 antioxidant axis and suppressing mitochondria-dependent apoptosis. Thus, the development of this probe has great potential for early and rapid prediction of IPF progression and improved treatment.