Exosome-Biomimetic Nanoprobes Achieve Ultrasensitive Detection and Real-Time Monitoring of Liver Metastasis

Background ​​: Liver metastasis (LM) remains a leading cause of cancer mortality, with conventional imaging modalities suffering from physiological interference and insufficient sensitivity. Fluorine-19 (¹⁹F) MRI offers a promising solution due to its negligible endogenous background, yet existing targeted probes face limitations in tumor heterogeneity and receptor variability. ​​ Methods ​​: We developed exosome-biomimetic nanoparticles (EP-NPs) by coating perfluorocarbon nanoparticles (PFCE NPs) with exosomal membranes derived from HEK-293T cells. The hybrid platform combined the targeting capability of exosomes with the high sensitivity of ¹⁹F MRI. Characterization included dynamic light scattering, transmission electron microscopy, and ¹⁹F NMR. In vitro cellular uptake was evaluated in BT-549 and NCI-H446 cells using confocal microscopy. In vivo targeting efficiency and biodistribution were assessed in a BT-549 liver metastasis mouse model via ¹⁹F/¹H MRI. Toxicity was tested via MTT assays, serum biochemistry, and histopathology. ​​ Results ​​: EP-NPs exhibited a hydrodynamic diameter of 111.6 ± 8.2 nm, negative zeta potential (-20.50 mV), and stable ¹⁹F signal. Confocal imaging confirmed enhanced cellular uptake compared to non-targeted PFCE NPs. In vivo , EP-NPs enabled precisely and early detection of LM with sustained ¹⁹F signal. Biodistribution revealed accumulation in the liver and spleen, and toxicity assessments demonstrated no significant hepatorenal impairment or histological damage. ​​ Conclusion ​​: EP-NPs integrate exosomal targeting and ¹⁹F MRI to achieve ultrasensitive LM detection with high biocompatibility and prolonged circulation. This platform holds potential for real-time monitoring of metastatic progression and clinical translation, overcoming limitations of conventional imaging agents.