Ultrasound and microbubble induced release from intracellular compartments

BACKGROUND Ultrasound and microbubbles (USMB) have been shown to enhance the intracellular uptake of molecules, generally thought to occur as a result of sonoporation. The underlying mechanism associated with USMB-enhanced intracellular uptake such as membrane disruption and endocytosis may also be associated with USMB-induced release of cellular materials to the extracellular milieu. This study investigates USMB effects on the molecular release from cells through membrane-disruption and exocytosis. RESULTS USMB induced the release of 19% and 67% of GFP from the cytoplasm in viable and non-viable cells, respectively. Tfn release from early/recycling endosomes increased by 23% in viable cells upon USMB treatment. In addition, the MFI of LAMP-1 antibody increased by 50% in viable cells, suggesting USMB-stimulated lysosome exocytosis. In non-viable cells, labeling of LAMP-1 intracellular structures in the absence of cell permeabilization by detergents suggests that USMB-induced cell death correlates with lysosomal permeabilization. CONCLUSIONS In conclusion, USMB enhanced the molecular release from the cytoplasm, lysosomes, and early/recycling endosomes.