Dual-Targeting Near-Infrared Fluorescent Probe for Simultaneous Mitochondrial Injury Assessment and Fibrosis Monitoring in Pulmonary Fibrosis

Mitochondria and the endoplasmic reticulum (ER) are pivotal organelles that maintain cellular homeostasis; their dysfunction initiates pathological cascades associated with both fibrosis and oncogenesis. Bleomycin (BLM), a widely utilized anticancer drug, inhibits tumor growth by inducing DNA damage. However, its clinical application is constrained by severe pulmonary toxicity. Here, we develop a novel fluorescent probe, BDSTI. In contrast to existing probes that target a single organelle, BDSTI allows for efficient colocalization of mitochondria and ER, facilitating the synchronous observation of their interactions. It also exhibits the capability to detect intracellular polarity and viscosity dynamics induced by BLM concentration gradients. BLM disrupts mitochondrial membrane potential and triggers the accumulation of reactive oxygen species (ROS). High-resolution imaging further confirms its role in inducing mitochondrial morphological abnormalities. Notably, BDSTI enables the visualization of BLM-induced lung injury through in vivo and ex vivo imaging of pulmonary fibrosis models in tumor-bearing mice. Notably, BDSTI enables visualization of BLM-induced lung injury through in vivo and ex vivo imaging of pulmonary fibrosis models in tumor-bearing mice. Furthermore, this probe serves as a functional tool to evaluate the therapeutic efficacy of various ER stress inhibitors in mitigating BLM-mediated pulmonary damage.