Exosomal lipidomic alterations as prospective molecular signatures for radiation emergencies

In radiological and nuclear emergency scenarios, it is crucial to quantify the dose of ionizing radiation exposure. The conventional biodosimetry techniques, such as dicentric assays, are time and resource intensive for widespread usage. Exosomes being stable extracellular vesicles bearing molecular cargo can offer a promising alternative for minimally invasive, high-throughput biodosimetry. In the current study, plasma-derived exosomes were isolated using ultracentrifugation in Sprague Dawley rats at 24h, 48h, and 72h following gamma irradiation 2, 5 and 8 Gy. Exosomes were characterized using transmission electron microscopy, dynamic light scattering and western blotting. The untargeted LC-MS lipidomic profiling was conducted to detect alterations in lipid species. The lipid analysis revealed dose and time dependent changes characterized by increased levels of polyunsaturated fatty acids, ceramide phosphoethanolamines, fatty esters, phosphatidylcholines, and sterols, alongside depletion of antioxidant plasmalogens and triglycerides. These lipidomic alterations indicate radiation-induced oxidative stress, membrane remodeling, and apoptotic signaling conveyed through exosomes. A candidate panel of lipid biomarkers showing robust responsiveness to dose and time was identified, offering minimally invasive tool for radiation biodosimetry and triage during emergency scenarios thereby facilitating improved assessment and management of radiological exposures.