Augmentation of cardiac protein delivery using ultrasound targeted microbubble destruction.
Gas-filled microbubbles have become an important tool as ultrasonic contrast agents. We have previously shown that ultrasound-targeted microbubble destruction (UTMD) can direct plasmids to the heart. The aim of this study was to evaluate UTMD for protein delivery. Six different groups of rats received 1 microg of luciferase protein with varying protocols: (1) luciferase-loaded microbubbles and ultrasound; (2) luciferase only; (3) luciferase and ultrasound; (4) luciferase-loaded microbubbles; (5) unloaded microbubbles incubated with luciferase and ultrasound; (6) unloaded microbubbles with ultrasound followed by luciferase. Relative luminescence units per mg protein per s were determined in hearts and control organs. The rats that received ultrasound and luciferase-loaded bubbles showed a six-fold higher cardiac luciferase uptake compared with control groups that did not include bubbles. None of the other groups significantly augmented cardiac luciferase activity. We conclude that ultrasound-targeted microbubble destruction can substantially and noninvasively augment organ-specific delivery of proteins.
Bekeredjian
Raffi
R
Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, NB 11.200, Dallas, TX 75390-8573, USA.
Chen
Shuyuan
S
Grayburn
Paul A
PA
Shohet
Ralph V
RV
D000818:Animals; D003287:Contrast Media; D004452:Echocardiography; D006321:Heart; D008156:Luciferases / Q000008:administration & dosage*; D008164:Luminescent Proteins / Q000008:administration & dosage*; D045423:Microbubbles; D051381:Rats; D014465:Ultrasonics
D003287:Contrast Media; D008164:Luminescent Proteins; D008156:Luciferases