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Ultrasound-Targeted Microbubble Destruction for Cardiac Gene Delivery

Protocol
First Online:
Part of the Methods in Molecular Biology book series (MIMB, volume 1521)

Abstract

Ultrasound targeted microbubble destruction (UTMD) is a novel technique that is used to deliver a gene or other bioactive substance to organs of living animals in a noninvasive manner. Plasmid DNA binding with cationic liposome into nanoparticles are assembled into the shell of microbubbles, which are circulated by intravenous injection. Intermittent bursts of ultrasound with low frequency and high mechanical index destroys the microbubbles and releases the nanoparticles into targeted organ to transfect local organ cells. Cell-specific promoters can be used to further enhance cell specificity. Here we describe UTMD applied to cardiac gene delivery.

Key words

Gene Gene delivery Microbubble Ultrasound Ultrasound targeted microbubble destruction 
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Notes

Acknowledgment

This work was supported by the Mark Shepherd Endowment of The Baylor Foundation

References

  1. 1.
    Shohet RV, Chen S, Zhou YT, Wang Z, Meidell RS, Unger RH et al (2000) Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation 101:2554–2556CrossRefPubMedGoogle Scholar
  2. 2.
    Chen S, Wang Z, Zhou YT, Grayburn PA (2000) Optimization of the size distribution and myocardial contrast effect of perfluorocarbon-filled albumin microbubbles by lyophilization under continuous negative pressure. J Am Soc Echocardiogr 13:748–753CrossRefPubMedGoogle Scholar
  3. 3.
    Frenkel PA, Chen S, Thai T, Shohet RV, Grayburn PA (2002) DNA-loaded albumin microbubbles enhance ultrasound-mediated transfection in vitro. Ultrasound Med Biol 28:817–822CrossRefPubMedGoogle Scholar
  4. 4.
    Chen S, Kroll MH, Shohet RV, Frenkel P, Mayer SA, Grayburn PA (2002) Bioeffects of myocardial contrast microbubble destruction by echocardiography. Echocardiography 19:495–500CrossRefPubMedGoogle Scholar
  5. 5.
    Chen S, Shohet RV, Bekeredjian R, Frenkel P, Grayburn PA (2003) Optimization of ultrasound parameters for cardiac gene delivery of adenoviral or plasmid deoxyribonucleic acid by ultrasound-targeted microbubble destruction. J Am Coll Cardiol 42:301–308CrossRefPubMedGoogle Scholar
  6. 6.
    Bekeredjian R, Chen S, Frenkel PA, Grayburn PA, Shohet RV (2003) Ultrasound-targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart. Circulation 108:1022–1026CrossRefPubMedGoogle Scholar
  7. 7.
    Bekeredjian R, Chen S, Pan W, Grayburn PA, Shohet RV (2004) Effects of ultrasound-targeted microbubble destruction on cardiac gene expression. Ultrasound Med Biol 30:539–543CrossRefPubMedGoogle Scholar
  8. 8.
    Korpanty G, Chen S, Shohet RV, Ding J, Yang B, Frenkel PA et al (2005) Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles. Gene Ther 12:1305–1312CrossRefPubMedGoogle Scholar
  9. 9.
    Bekeredjian R, Chen S, Grayburn PA, Shohet RV (2005) Augmentation of cardiac protein delivery using ultrasound targeted microbubble destruction. Ultrasound Med Biol 31:687–691CrossRefPubMedGoogle Scholar
  10. 10.
    Chen S, Shimoda M, Chen J, Grayburn PA (2013) Stimulation of adult resident cardiac progenitor cells by durable myocardial expression of thymosin beta 4 with ultrasound-targeted microbubble delivery. Gene Ther 20:225–233CrossRefPubMedGoogle Scholar
  11. 11.
    Chen S, Chen J, Huang P, Meng X, Clayton S, Shen J et al (2015) Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction. Biochem Biophys Res Commun 458:823–829CrossRefPubMedGoogle Scholar
  12. 12.
    Li L, Wu S, Liu Z, Zhuo Z, Tan K, Xia H et al (2015) Ultrasound-targeted microbubble destruction improves the migration and homing of mesenchymal stem cells after myocardial infarction by upregulating SDF-1/CXCR4: a pilot study. Stem Cells Int 2015:691310PubMedPubMedCentralGoogle Scholar
  13. 13.
    Deng Q, Hu B, Cao S, Song HN, Chen JL, Zhou Q (2015) Improving the efficacy of therapeutic angiogenesis by UTMD-mediated Ang-1 gene delivery to the infarcted myocardium. Int J Mol Med 36:335–344PubMedPubMedCentralGoogle Scholar
  14. 14.
    Liao YY, Chen ZY, Wang YX, Lin Y, Yang F, Zhou QL (2014) New progress in angiogenesis therapy of cardiovascular disease by ultrasound targeted microbubble destruction. Biomed Res Int 2014:872984PubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhao YZ, Tian XQ, Zhang M, Cai L, Ru A, Shen XT et al (2014) Functional and pathological improvements of the hearts in diabetes model by the combined therapy of bFGF-loaded nanoparticles with ultrasound-targeted microbubble destruction. J Control Release 186:22–31CrossRefPubMedGoogle Scholar
  16. 16.
    Wang HB, Yang L, Wu J, Sun L, Wu J, Tian H et al (2014) Reduced ischemic injury after stroke in mice by angiogenic gene delivery via ultrasound-targeted microbubble destruction. J Neuropathol Exp Neurol 73:548–558CrossRefPubMedGoogle Scholar
  17. 17.
    Yan P, Chen KJ, Wu J, Sun L, Sung HW, Weisel RD et al (2014) The use of MMP2 antibody-conjugated cationic microbubble to target the ischemic myocardium, enhance Timp3 gene transfection and improve cardiac function. Biomaterials 35:1063–1073CrossRefPubMedGoogle Scholar
  18. 18.
    Ling ZY, Shu SY, Zhong SG, Luo J, Su L, Liu ZZ et al (2013) Ultrasound targeted microbubble destruction promotes angiogenesis and heart function by inducing myocardial microenvironment change. Ultrasound Med Biol 39:2001–2010CrossRefPubMedGoogle Scholar
  19. 19.
    Chen ZY, Lin Y, Yang F, Jiang L, Ge SP (2013) Gene therapy for cardiovascular disease mediated by ultrasound and microbubbles. Cardiovasc Ultrasound 11:11CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Sun L, Huang CW, Wu J, Chen KJ, Li SH, Weisel RD et al (2013) The use of cationic microbubbles to improve ultrasound-targeted gene delivery to the ischemic myocardium. Biomaterials 34:2107–2116CrossRefPubMedGoogle Scholar
  21. 21.
    Vu V, Liu Y, Sen S, Xu A, Sweeney G (2013) Delivery of adiponectin gene to skeletal muscle using ultrasound targeted microbubbles improves insulin sensitivity and whole body glucose homeostasis. Am J Physiol Endocrinol Metab 304:E168–E175CrossRefPubMedGoogle Scholar
  22. 22.
    Walton CB, Anderson CD, Boulay R, Shohet RV (2011) Introduction to the ultrasound targeted microbubble destruction technique. J Vis Exp pii: 2963Google Scholar
  23. 23.
    Fujii H, Li SH, Wu J, Miyagi Y, Yau TM, Rakowski H et al (2011) Repeated and targeted transfer of angiogenic plasmids into the infarcted rat heart via ultrasound targeted microbubble destruction enhances cardiac repair. Eur Heart J 32:2075–2084CrossRefPubMedGoogle Scholar
  24. 24.
    Fujii H, Sun Z, Li SH, Wu J, Fazel S, Weisel RD et al (2009) Ultrasound-targeted gene delivery induces angiogenesis after a myocardial infarction in mice. JACC Cardiovasc Imaging 2:869–879CrossRefPubMedGoogle Scholar
  25. 25.
    Geis NA, Mayer CR, Kroll RD, Hardt SE, Katus HA, Bekeredjian R (2009) Spatial distribution of ultrasound targeted microbubble destruction increases cardiac transgene expression but not capillary permeability. Ultrasound Med Biol 35:1119–1126CrossRefPubMedGoogle Scholar
  26. 26.
    Vancraeynest D, Havaux X, Pouleur AC, Pasquet A, Gerber B, Beauloye C et al (2006) Myocardial delivery of colloid nanoparticles using ultrasound-targeted microbubble destruction. Eur Heart J 27:237–245CrossRefPubMedGoogle Scholar
  27. 27.
    Yuan QY, Huang J, Chu BC, Li XJ, Li XS, Si LY (2012) A targeted high-efficiency angiogenesis strategy as therapy for myocardial infarction. Life Sci 90:695–702CrossRefPubMedGoogle Scholar
  28. 28.
    Su CH, Wu YJ, Wang HH, Yeh HI (2012) Nonviral gene therapy targeting cardiovascular system. Am J Physiol Heart Circ Physiol 303:H629–H638CrossRefPubMedGoogle Scholar
  29. 29.
    Yuan QY, Huang J, Li XJ, Li XS, Si LY (2013) Transendocardial delivery of HGF via microbubbles and ultrasound to treat acute myocardial infarction. Curr Gene Ther 13:31–38CrossRefPubMedGoogle Scholar
  30. 30.
    Castle J, Butts M, Healey A, Kent K, Marino M, Feinstein SB (2013) Ultrasound-mediated targeted drug delivery: recent success and remaining challenges. Am J Physiol Heart Circ Physiol 304:H350–H357CrossRefPubMedGoogle Scholar
  31. 31.
    Dörner J, Struck R, Zimmer S, Peigney C, Duerr GD, Dewald O et al (2013) Ultrasound-mediated stimulation of microbubbles after acute myocardial infarction and reperfusion ameliorates left-ventricular remodelling in mice via improvement of borderzone vascularization. PLoS One 8:e56841CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Unger E, Porter T, Lindner J, Grayburn P (2014) Cardiovascular drug delivery with ultrasound and microbubbles. Adv Drug Deliv Rev 72:110–126CrossRefPubMedGoogle Scholar
  33. 33.
    Sanches PG, Mühlmeister M, Seip R, Kaijzel E, Löwik C, Böhmer M et al (2014) Ultrasound-mediated gene delivery of naked plasmid DNA in skeletal muscles: a case for bolus injections. J Control Release 195:130–137CrossRefPubMedGoogle Scholar
  34. 34.
    Korpisalo P, Hytönen JP, Laitinen JT, Närväinen J, Rissanen TT, Gröhn OH et al (2014) Ultrasound imaging with bolus delivered contrast agent for the detection of angiogenesis and blood flow irregularities. Am J Physiol Heart Circ Physiol 307:H1226–H1232CrossRefPubMedGoogle Scholar
  35. 35.
    Liu Y, Li L, Su Q, Liu T, Ma Z, Yang H (2015) Ultrasound-Targeted Microbubble Destruction Enhances Gene Expression of microRNA-21 in Swine Heart via Intracoronary Delivery. Echocardiography 32:1407–1416CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Division of Cardiology, Department of Internal Medicine, Baylor Heart and Vascular InstituteBaylor University Medical CenterDallasUSA

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