Development and characterization of acoustically responsive exosomes for simultaneous imaging and drug delivery applications

Exosomes are naturally secreted bilayer vesicles ranging in size from 40 to 200 nm that play a critical role in cell-to-cell communications and protein and RNA delivery. Researchers have explored exosomes as potential drug delivery vehicles due to their natural morphology and small size. Here, for the first time, bovine milk derived exosomes have been modified to be acoustically responsive as potential ultrasound contrast agents or a drug carrier. The echogenic exosomes were formed through a freeze-drying process in the presence of mannitol. The size and morphology of the particles were assessed with a qNano™ and atomic force microscopy (AFM). The ultrasound response of these particles was characterized through linear and non-linear scattering behaviors. The presence of the echogenic exosomes enhances the scattered signal by 11.4 ± 6.3 dB. The stability of these particles under constant ultrasound exposure were assessed to be similar to that of echogenic polymersomes. The variation of mannitol concentration was assessed. To assess the imaging improvement of ultrasound imaging, the exosomes were injected through a tail vein in mice. The modification of the echogenic exosomes shows to have great promise as potential ultrasound contrast agents or ultrasound responsive drug delivery system.