Intracellular delivery and calcium transients generated in sonoporation facilitated by microbubbles

Ultrasound application in the presence of microbubbles is a promising strategy for intracellular drug and gene delivery, but it may also trigger other cellular responses. This study investigates the relationship between the change of cell membrane permeability generated by ultrasound-driven microbub...

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Bibliographic Details
Published in:Journal of controlled release 2010-02, Vol.142 (1), p.31-39
Main Authors: FAN, Z, KUMON, R. E, PARK, J, DENG, C. X
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Calcium (intracellular)
Calcium - administration & dosage
Calcium permeability
Calcium signalling
Cell Line
Cell Membrane Permeability
Cell membranes
Cell Survival
Controlled release
Drug delivery
Drug Delivery Systems - methods
Fura-2
Gene transfer
General pharmacology
Medical sciences
Membrane permeability
Microbubbles
Myoblasts, Cardiac - cytology
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Pores
propidium iodide
Rats
Ultrasonics
Ultrasound
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Summary:Ultrasound application in the presence of microbubbles is a promising strategy for intracellular drug and gene delivery, but it may also trigger other cellular responses. This study investigates the relationship between the change of cell membrane permeability generated by ultrasound-driven microbubbles and the changes in intracellular calcium concentration ([Ca(2+)](i)). Cultured rat cardiomyoblast (H9c2) cells were exposed to a single ultrasound pulse (1MHz, 10-15cycles, 0.27MPa) in the presence of a Definity(TM) microbubble. Intracellular transport via sonoporation was assessed in real time using propidium iodide (PI), while [Ca(2+)](i) and dye loss from the cells were measured with preloaded fura-2. The ultrasound exposure generated fragmentation or shrinking of the microbubble. Only cells adjacent to the ultrasound-driven microbubble exhibited propidium iodide uptake with simultaneous [Ca(2+)](i) increase and fura-2 dye loss. The amount of PI uptake was correlated with the amount of fura-2 dye loss. Cells with delayed [Ca(2+)](i) transients from the time of ultrasound application had no uptake of PI. These results indicate the formation of non-specific pores in the cell membrane by ultrasound-stimulated microbubbles and the generation of calcium waves in surrounding cells without pores.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2009.09.031