Goat milk-derived exosomes engineered for multi-modal imaging of pancreatic cancer

Introduction: Pancreatic cancer seriously endangers the safety of human life. In this study, goat milk-derived exosomes (GEx), the nature nanocarriers were used to engineer an GEx-based nanoprobe for multimodal PET/CT and near-infrared fluorescence (NIRF) imaging of Pancreatic cancer.

Methods: GEx were separated by differential ultracentrifugation from goat milk and examined using TEM (transmission electron microscopy) and DLS (dynamic light scattering). The ability of GEx to combine pancreatic tumor cells was illustrated by confocal microscopy. GEx@ICG (indocyanine green) was fabricated by mixing GEx with ICG in PBS and incubating in the dark . Using hydrophobic insertion approach, DSPE-PEG₂₀₀₀-N₃ was incubated with GEx@ICG to form N₃-PEG₂₀₀₀-DSPE-GEx@ICG(N₃-GEx@ICG). The samples were passed through centrifugal filter devices before further use. The toxicity of N₃-GEx@ICG in vitro were assessed by CCK8 assay. N₃-GEx@ICG was injected into the subcutaneous murine pancreatic cancer model through tail veins for NIRF imaging at different times. N₃-GEx@ICG was injected into orthotopic murine pancreatic cancer model (n = 3 per group) at pre-targeting time points (24 h). ⁶⁸Ga-L-NETA-DBCO was injected into the mice via the tail vein. Mice were anesthetized for micro-PET static imaging based on “click chemistry” at 1 and 2 h after the injection of ⁶⁸Ga-L-NETA-DBCO.

Results: In this study, GEx was successfully separated from goat milk. Transmission electron microscope confirmed that GEx has a lipid bilayer structure. The hydrated particle sizes of GEx and N₃-GEx@ICG were 140.83±0.73 and 201.21±0.87 nm. Confocal experiments have observed that GEx has good binding ability to tumor cells. NIRF images in vivo showed that the injection of N₃-GMV@ICG group could detect stronger fluorescence signal at the tumor site than the free ICG group, and the fluorescence signal was the strongest at 24 h. Clear tumor development was also observed on PET/CT images in vivo. No obvious signs of damage to major organs were observed in each group.

Conclusions: As an integrated diagnosis and treatment probe, N₃-GEx@ICG successfully realized the PET/CT/NIRF multimodal imaging of pancreatic cancer. The curative effect is remarkable and it has a broad clinical transformation prospect.

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