Exosome-encapsulated perfluorocarbon nanoprobes for precise imaging and persistent monitoring of liver metastasis

Liver metastasis (LM) remains a leading cause of cancer mortality, and conventional magnetic resonance imaging (MRI) is susceptible to physiological interference, which affects the diagnostic accuracy of LM. 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. We developed a novel ¹⁹F MRI 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 superiority of ¹⁹F MRI. Characterization included dynamic light scattering, transmission electron microscopy, and 19F nuclear magnetic resonance (NMR). In vitro cellular uptake was evaluated in BT-549 and NCI-H446 cells using confocal microscopy. In vivo targeting ¹⁹F MRI study was assessed in a BT-549 liver metastasis mouse model. Toxicity was tested via 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, serum biochemistry, and histopathology. 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 of EP-NPs compared to non-targeted PFCE NPs. In vivo, EP-NPs enabled precisely detection of LM with sustained ¹⁹F signal. Biodistribution revealed that EP-NPs accumulate in the liver and spleen, and toxicity assessments demonstrated no significant hepatorenal impairment or histological damage. EP-NPs integrate priorities of exosomes and ¹⁹F MRI achieve precise LM detection with high biocompatibility and prolonged circulation. This platform holds potential for clinical translation, overcoming limitations of conventional imaging agents.