Targeted gene transfection from microbubbles into vascular smooth muscle cells using focused, ultrasound-mediated delivery.
We investigated a method for gene delivery to vascular smooth muscle cells using ultrasound triggered delivery of plasmid DNA from electrostatically coupled cationic microbubbles. Microbubbles carrying reporter plasmid DNA were acoustically ruptured in the vicinity of smooth muscle cells in vitro under a range of acoustic pressures (0 to 950 kPa) and pulse durations (0 to 100 cycles). No effect on gene transfection or viability was observed from application of microbubbles, DNA or ultrasound alone. Microbubbles in combination with ultrasound (500-kPa, 1-MHz, 50-cycle bursts at a pulse repetition frequency [PRF] of 100 Hz) significantly reduced viability both with DNA (53 +/- 27%) and without (19 +/- 8%). Maximal gene transfection ( approximately 1% of cells) occurred using 50-cycle, 1-MHz pulses at 300 kPa, which resulted in 40% viability of cells. We demonstrated that we can locally deliver DNA to vascular smooth muscle cells in vitro using microbubble carriers and focused ultrasound.
Phillips
Linsey C
LC
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Klibanov
Alexander L
AL
Wamhoff
Brian R
BR
Hossack
John A
JA
D000818:Animals; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D045423:Microbubbles; D009131:Muscle, Smooth, Vascular / Q000000981:diagnostic imaging*; D010957:Plasmids; D051381:Rats; D014463:Ultrasonography
Adv Drug Deliv Rev. 2004 May 7;56(9):1291-314
15109770
J Acoust Soc Am. 2001 Jul;110(1):588-96
11508983
Gene Ther. 2000 Dec;7(23):2023-7
11175314
Annu Rev Biomed Eng. 2007;9:415-47
17651012
Ultrasound Med Biol. 2006 Aug;32(8):1269-79
16875960
Prog Cardiovasc Dis. 2001 Jul-Aug;44(1):45-54
11533926
Hum Gene Ther. 1996 Jul 10;7(11):1339-46
8818721
Ultrasound Med Biol. 2009 May;35(5):847-60
19110370
Ultrasound Med Biol. 2008 Nov;34(11):1857-67
18524464
Biochem Biophys Res Commun. 1994 Sep 30;203(3):1622-8
7945312
Circ Res. 2009 Mar 13;104(5):679-87
19168443
J Vasc Res. 2010;47(3):270-4
19923850
Physiol Rev. 2004 Jul;84(3):767-801
15269336
JAMA. 2007 Jan 10;297(2):159-68
17148711
IEEE Trans Ultrason Ferroelectr Freq Control. 1999;46(1):220-32
18238417
J Gene Med. 2009 Aug;11(8):729-36
19455570
J Acoust Soc Am. 2002 Mar;111(3):1460-4
11931323
Gene Ther. 2006 Jan;13(2):163-72
16177822
Ultrasound Med Biol. 2003 Apr;29(4):601-7
12749930
Lab Invest. 1983 Aug;49(2):208-15
6876748
Drug Saf. 2009;32(9):749-70
19670915
J Gene Med. 2006 Nov;8(11):1347-57
16981246
Biochem Biophys Res Commun. 2007 Aug 10;359(4):860-5
17568561
Ultrasound Med Biol. 2004 Apr;30(4):527-38
15121255
Invest Radiol. 1997 Dec;32(12):723-7
9406011
Circulation. 2007 Mar 20;115(11):1440-55; discussion 1455
17344324
Circulation. 2002 Mar 12;105(10):1233-9
11889019
J Drug Target. 2007 Dec;15(10):664-71
18041634
Phys Med Biol. 2006 Aug 21;51(16):4031-45
16885622
Adv Drug Deliv Rev. 2008 Jun 30;60(10):1177-92
18474407
Gene Ther. 2000 Nov;7(21):1833-9
11110415
Ultrasound Med Biol. 1998 May;24(4):587-95
9651968
Ultrasound Med Biol. 2003 Dec;29(12):1759-67
14698343
J Acoust Soc Am. 2001 Jul;110(1):597-606
11508985
Arterioscler Thromb Vasc Biol. 2009 Feb;29(2):225-31
19023090
Cancer Sci. 2006 Oct;97(10):1111-4
16925580