The status and prospect of ultrasound and microbubble-mediated gene delivery in cardiovascular disease gene therapy_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

QIN Xionghai , KANG Kai , SUN Lu ,  TIAN Hai ,  JIANG Shulin

Department of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, P.R.China;

Corresponding?author：

TIAN Hai, Email: doctor_tianhai@163.com; JIANG Shulin, Email: sljiang36@163.com

Keywords：

Cardiovascular disease; gene therapy; delivery; targeted ultrasound microbubble destruction; ultrasound-mediated gene delivery

DOI：

10.7507/1007-4848.201612044

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

With the development of molecular and cellar cardiology, gene therapy to cardiovascular disease has become the hot spot and the direction of study. Now, preclinical studies on ultrasound-mediated gene delivery (UMGD) in cardiovascular disease have achieved some success, but it is still hindered by a series of practical challenges for clinical translation. Even so, UMGD still holds the promise to cardiovascular disease in gene therapy for its non-invasiveness, accuracy, safety and ability to deliver multiple genes with repeated deliveries. In this review, we will focus on the basic principle, the current development, the future prospect and drawbacks of UMGD in the therapeutic applications of cardiovascular disease.

Citation： QIN Xionghai, KANG Kai, SUN Lu, TIAN Hai, JIANG Shulin. The status and prospect of ultrasound and microbubble-mediated gene delivery in cardiovascular disease gene therapy. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2018, 25(3): 256-261. doi: 10.7507/1007-4848.201612044 Copy

1.	Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation, 2015, 131(4): e29-322.
2.	O’Neill BJ, Rana SN, Bowman V. An integrated approach for vascular health: a call to action. Can J Cardiol, 2015, 31(1): 99-102.
3.	Rincon MY, VandenDriessche T, Chuah MK. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation. Cardiovasc Res, 2015, 108(1): 4-20.
4.	Tilemann L, Ishikawa K, Weber T, et al. Gene therapy for heart failure. Circ Res, 2012, 110(5): 777-793.
5.	Rapti K, Chaanine AH, Hajjar RJ. Targeted gene therapy for the treatment of heart failure. Can J Cardiol, 2011, 27(3): 265-283.
6.	Shohet RV, Chen S, Zhou YT, et al. Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation, 2000, 101(22): 2554-2556.
7.	Panje CM, Wang DS, Willmann JK. Ultrasound and microbubblemediated gene delivery in cancer: progress and perspectives. Invest Radiol, 2013, 48(11): 755-769.
8.	Unger E, Porter T, Lindner J, et al. Cardiovascular drug delivery with ultrasound and microbubbles. Adv Drug Deliv Rev, 2014, 72: 110-126.
9.	Carson AR, McTiernan CF, Lavery L, et al. Ultrasound-targeted microbubble destruction to deliver siRNA cancer therapy. Cancer Res, 2012, 72(23): 6191-6199.
10.	Castle J, Butts M, Healey A, et al. Ultrasound-mediated targeted drug delivery: recent success and remaining challenges. Am J Physiol Heart Circ Physiol, 2013, 304(3): H350-H357.
11.	Cao WJ, Matkar PN, Chen HH, et al. Microbubbles and ultrasound: therapeutic applications in diabetic nephropathy. Adv Exp Med Biol, 2016, 880: 309-330.
12.	Bazan-Peregrino M, Arvanitis CD, Rifai B, et al. Ultrasound-induced cavitation enhances the delivery and therapeutic efficacy of an oncolytic virus in an in vitro model. J Control Release, 2012, 157(2): 235-242.
13.	馮若. 超聲空化與超聲醫學. 中華超聲影像學雜志, 2004, 13(1): 63-65.
14.	鐘渝, 劉政. 超聲空化效應在治療領域中的研究進展. 臨床超聲醫學雜志, 2016, 18(4): 256-258.
15.	Prentice P, Cuschieri A, Dholakia K, et al. Membrane disruption byoptically controlled microbubble Cavitation. Nature Physics, 2005, 1(2): 107-110.
16.	李立華, 曹軍英, 王占江. 醫學超聲微泡造影劑空化效應的研究進展.臨床超聲醫學雜志, 2014, 16(1): 41-44．.
17.	牟蕓, 姚磊, 鄭哲嵐, 等. 2006 年浙江省超聲醫學學術年會論文匯編. 2006．.
18.	劉珊, 伍烽, 鄒建中, 等. 連續和脈沖高強度聚焦超聲輻照離體牛晶狀體致凝固性壞死的變化過程. 中國介入影像與治療學, 2015, 12(6): 361-365.
19.	劉珊. 空化效應和血流對脈沖 HIFU 消融治療的影響. 重慶醫科大學, 2015. 1-20.
20.	Deshpande N, Needles A, Willmann JK. Molecular ultrasound imaging: current status and future directions. Clin Radiol, 2010, 65(7): 567-581.
21.	Stride E. Physical principles of microbubbles for ultrasound imaging and therapy. Front Neurol Neurosci, 2015, 36: 11-22.
22.	Gramiak R, Shah PM. Echocardiography of the aortic root. Invest Radiol, 1968, 3(5): 356-366.
23.	香麗萍, 穆玉明. 靶向超聲造影劑在干細胞移植中的研究進展. 海南醫學, 2015, 26(6): 843-846.
24.	王夢, 穆玉明. 靶向超聲造影劑在冠心病中的應用. 醫學研究雜志, 2015, 44(7): 4-6.
25.	唐紅. 靶向超聲造影劑在心血管領域的研究現狀與展望. 西部醫學, 2013, 25(4): 481-483.
26.	Shohet RV, Grayburn PA. Potential bioeffects of ultrasonic destruction of microbubble contrast agents. J Am Coll Cardiol, 2006, 47(7): 1469-a1470.
27.	Gaspar V, De Melo-Diogo D, Costa E, et al. Minicircle DNA vectors for gene therapy: advances and applications. Expert Opin Biol Ther, 2015, 15(3): 353-379.
28.	Bekeredjian R, Chen S, Frenkel PA, et al. Ultrasound-targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart. Circulation, 2003, 108(8): 1022-1026.
29.	Kondo I, Ohmori K, Oshita A, et al. Treatment of acute myocardial infarction by hepatocyte growth factor gene transfer: the first demonstration of myocardial transfer of a " functional” gene using ultrasonic microbubble destruction. J Am Coll Cardiol, 2004, 44 (3): 644-653.
30.	Fujii H, Sun Z, Li SH, et al. Ultrasound-targeted gene delivery induces angiogenesis after a myocardial infarction in mice. JACC Cardiovasc Imaging, 2009, 2(7): 869-879.
31.	Fujii H, Li SH, Wu J, et al. Repeated and targeted transfer of angiogenic plasmids into the infarcted rat heart via ultrasound targeted microbubble destruction enhances cardiac repair. Eur Heart J, 2011, 32(16): 2075-2084.
32.	曹治寰, 曹省, 宋宏寧, 等. 超聲靶向破壞陽離子微泡介導 SDF-1α 基因轉染提高外源性血管新生效應的研究. 臨床超聲醫學雜志, 2015, 17(5):289-292.
33.	崔晶晶, 曹省陳, 金玲, 等. 核定位信號肽在超聲靶向破壞微泡介導基因轉染治療犬心肌梗死中的促進作用. 臨床超聲醫學雜志, 2017, 19(1): 1-6.
34.	鄧傾. 超聲靶向破壞陽離子微泡聯合 NFκB 核定位基序促進 SDF-1α 基因轉染治療心肌梗死. 武漢大學, 2014. 1-20.
35.	Cui K, Yan T, Luo Q, et al. Ultrasound microbubble-mediated delivery of integrin-linked kinase gene improves endothelial progenitor cells dysfunction in pre-eclampsia. DNA Cell Biol, 2014, 33(5): 301-310.
36.	Kokhuis TJ, Skachkov I, Naaijkens BA, et al.Intravital microscopy of localized stem cell delivery using microbubbles and acoustic radiation force. Biotechnol Bioeng, 2015, 112(1): 220-227.
37.	李露. 微泡聯合超聲上調 SDF-1/CXCR4 促 MSCs 歸巢修復缺血心肌的實驗研究. 第三軍醫大學, 2015.1-20.
38.	Sun L, Huang CW, Wu J, et al. The use of cationic microbubbles to improve ultrasound-targeted gene delivery to the ischemic myocardium. Biomaterials, 2013, 34(8): 2107-2116.
39.	Lee PJ, Rudenko D, Kuliszewski MA, et al. Survivin gene therapy attenuates left ventricular systolic dysfunction in doxorubicin cardiomyopathyby reducing apoptosis and fibrosis. Cardiovasc Res, 2014, 101(3): 423-433.
40.	Chen S, Chen J, Huang P, et al. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction. Biochem Biophys Res Commun, 2015, 458(4):823-829.
41.	Liu Y, Li L, Su Q, et al. Ultrasound-targeted microbubble destruction enhances gene expression of microRNA-21 in Swine Heart via Intracoronary Delivery. Echocardiography, 2015, 32(9): 1407-1416.
42.	Su Q, Li L, Wang J, et al. Mechanism of programmed cell death factor 4/nuclear factor-κB signaling pathway in porcine coronary micro-embolization-induced cardiac dysfunction. Exp Biol Med (Maywood), 2015, 240(11): 1426-1433.
43.	Wang Y, Zhou J, Zhang Y, et al. Delivery of TFPI-2 using SonoVue and adenovirus results in the suppression of thrombosis and arterial re-stenosis. Exp Biol Med (Maywood), 2010, 235(9): 1072-1081.
44.	蘇強. 超聲微泡靶向介導 microRNA-21 調控 PDCD4/NF-κB/TNF-α 通路防治冠狀動脈微栓塞致心肌損傷機制的研究. 廣西醫科大學, 2015.1-20.
45.	Chen S, Ding J, Yu C, et al. Reversal of streptozotocin-induced diabetes in rats by gene therapy with betacellulin and pancreatic duodenal homeobox-1. Gene Ther, 2007, 14(14): 1102-1110.
46.	Chen S, Shimoda M, Wang MY, et al. Regeneration of pancreatic islets in vivo by ultrasound-targeted gene therapy. Gene Ther, 2010, 17(11): 1411-1420.
47.	Chen S, Shimoda M, Chen J, et al. Transient overexpression of cyclin D2/CDK4/GLP1 genes induces proliferation and differentiation of adult pancreatic progenitors and mediates islet regeneration. Cell Cycle, 2012, 11(4): 695-705.
48.	Chen S, Shimoda M, Chen J, et al. Ectopic transgenic expression of NKX2.2 induces differentiation of adult pancreatic progenitors and mediates islet regeneration. Cell Cycle, 2012, 11(8): 1544-1553.
49.	Chen S, Bastarrachea RA, Roberts BJ, et al. Successful beta cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1. Cell Cycle, 2014, 13(7): 1145-1151.
50.	Castle JW, Kent KP, Fan Y, et al. Therapeutic ultrasound: increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids. Atherosclerosis, 2015, 241(1): 92-99.

1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation, 2015, 131(4): e29-322.
2. O’Neill BJ, Rana SN, Bowman V. An integrated approach for vascular health: a call to action. Can J Cardiol, 2015, 31(1): 99-102.
3. Rincon MY, VandenDriessche T, Chuah MK. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation. Cardiovasc Res, 2015, 108(1): 4-20.
4. Tilemann L, Ishikawa K, Weber T, et al. Gene therapy for heart failure. Circ Res, 2012, 110(5): 777-793.
5. Rapti K, Chaanine AH, Hajjar RJ. Targeted gene therapy for the treatment of heart failure. Can J Cardiol, 2011, 27(3): 265-283.
6. Shohet RV, Chen S, Zhou YT, et al. Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation, 2000, 101(22): 2554-2556.
7. Panje CM, Wang DS, Willmann JK. Ultrasound and microbubblemediated gene delivery in cancer: progress and perspectives. Invest Radiol, 2013, 48(11): 755-769.
8. Unger E, Porter T, Lindner J, et al. Cardiovascular drug delivery with ultrasound and microbubbles. Adv Drug Deliv Rev, 2014, 72: 110-126.
9. Carson AR, McTiernan CF, Lavery L, et al. Ultrasound-targeted microbubble destruction to deliver siRNA cancer therapy. Cancer Res, 2012, 72(23): 6191-6199.
10. Castle J, Butts M, Healey A, et al. Ultrasound-mediated targeted drug delivery: recent success and remaining challenges. Am J Physiol Heart Circ Physiol, 2013, 304(3): H350-H357.
11. Cao WJ, Matkar PN, Chen HH, et al. Microbubbles and ultrasound: therapeutic applications in diabetic nephropathy. Adv Exp Med Biol, 2016, 880: 309-330.
12. Bazan-Peregrino M, Arvanitis CD, Rifai B, et al. Ultrasound-induced cavitation enhances the delivery and therapeutic efficacy of an oncolytic virus in an in vitro model. J Control Release, 2012, 157(2): 235-242.
13. 馮若. 超聲空化與超聲醫學. 中華超聲影像學雜志, 2004, 13(1): 63-65.
14. 鐘渝, 劉政. 超聲空化效應在治療領域中的研究進展. 臨床超聲醫學雜志, 2016, 18(4): 256-258.
15. Prentice P, Cuschieri A, Dholakia K, et al. Membrane disruption byoptically controlled microbubble Cavitation. Nature Physics, 2005, 1(2): 107-110.
16. 李立華, 曹軍英, 王占江. 醫學超聲微泡造影劑空化效應的研究進展.臨床超聲醫學雜志, 2014, 16(1): 41-44．.
17. 牟蕓, 姚磊, 鄭哲嵐, 等. 2006 年浙江省超聲醫學學術年會論文匯編. 2006．.
18. 劉珊, 伍烽, 鄒建中, 等. 連續和脈沖高強度聚焦超聲輻照離體牛晶狀體致凝固性壞死的變化過程. 中國介入影像與治療學, 2015, 12(6): 361-365.
19. 劉珊. 空化效應和血流對脈沖 HIFU 消融治療的影響. 重慶醫科大學, 2015. 1-20.
20. Deshpande N, Needles A, Willmann JK. Molecular ultrasound imaging: current status and future directions. Clin Radiol, 2010, 65(7): 567-581.
21. Stride E. Physical principles of microbubbles for ultrasound imaging and therapy. Front Neurol Neurosci, 2015, 36: 11-22.
22. Gramiak R, Shah PM. Echocardiography of the aortic root. Invest Radiol, 1968, 3(5): 356-366.
23. 香麗萍, 穆玉明. 靶向超聲造影劑在干細胞移植中的研究進展. 海南醫學, 2015, 26(6): 843-846.
24. 王夢, 穆玉明. 靶向超聲造影劑在冠心病中的應用. 醫學研究雜志, 2015, 44(7): 4-6.
25. 唐紅. 靶向超聲造影劑在心血管領域的研究現狀與展望. 西部醫學, 2013, 25(4): 481-483.
26. Shohet RV, Grayburn PA. Potential bioeffects of ultrasonic destruction of microbubble contrast agents. J Am Coll Cardiol, 2006, 47(7): 1469-a1470.
27. Gaspar V, De Melo-Diogo D, Costa E, et al. Minicircle DNA vectors for gene therapy: advances and applications. Expert Opin Biol Ther, 2015, 15(3): 353-379.
28. Bekeredjian R, Chen S, Frenkel PA, et al. Ultrasound-targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart. Circulation, 2003, 108(8): 1022-1026.
29. Kondo I, Ohmori K, Oshita A, et al. Treatment of acute myocardial infarction by hepatocyte growth factor gene transfer: the first demonstration of myocardial transfer of a " functional” gene using ultrasonic microbubble destruction. J Am Coll Cardiol, 2004, 44 (3): 644-653.
30. Fujii H, Sun Z, Li SH, et al. Ultrasound-targeted gene delivery induces angiogenesis after a myocardial infarction in mice. JACC Cardiovasc Imaging, 2009, 2(7): 869-879.
31. Fujii H, Li SH, Wu J, et al. Repeated and targeted transfer of angiogenic plasmids into the infarcted rat heart via ultrasound targeted microbubble destruction enhances cardiac repair. Eur Heart J, 2011, 32(16): 2075-2084.
32. 曹治寰, 曹省, 宋宏寧, 等. 超聲靶向破壞陽離子微泡介導 SDF-1α 基因轉染提高外源性血管新生效應的研究. 臨床超聲醫學雜志, 2015, 17(5):289-292.
33. 崔晶晶, 曹省陳, 金玲, 等. 核定位信號肽在超聲靶向破壞微泡介導基因轉染治療犬心肌梗死中的促進作用. 臨床超聲醫學雜志, 2017, 19(1): 1-6.
34. 鄧傾. 超聲靶向破壞陽離子微泡聯合 NFκB 核定位基序促進 SDF-1α 基因轉染治療心肌梗死. 武漢大學, 2014. 1-20.
35. Cui K, Yan T, Luo Q, et al. Ultrasound microbubble-mediated delivery of integrin-linked kinase gene improves endothelial progenitor cells dysfunction in pre-eclampsia. DNA Cell Biol, 2014, 33(5): 301-310.
36. Kokhuis TJ, Skachkov I, Naaijkens BA, et al.Intravital microscopy of localized stem cell delivery using microbubbles and acoustic radiation force. Biotechnol Bioeng, 2015, 112(1): 220-227.
37. 李露. 微泡聯合超聲上調 SDF-1/CXCR4 促 MSCs 歸巢修復缺血心肌的實驗研究. 第三軍醫大學, 2015.1-20.
38. Sun L, Huang CW, Wu J, et al. The use of cationic microbubbles to improve ultrasound-targeted gene delivery to the ischemic myocardium. Biomaterials, 2013, 34(8): 2107-2116.
39. Lee PJ, Rudenko D, Kuliszewski MA, et al. Survivin gene therapy attenuates left ventricular systolic dysfunction in doxorubicin cardiomyopathyby reducing apoptosis and fibrosis. Cardiovasc Res, 2014, 101(3): 423-433.
40. Chen S, Chen J, Huang P, et al. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction. Biochem Biophys Res Commun, 2015, 458(4):823-829.
41. Liu Y, Li L, Su Q, et al. Ultrasound-targeted microbubble destruction enhances gene expression of microRNA-21 in Swine Heart via Intracoronary Delivery. Echocardiography, 2015, 32(9): 1407-1416.
42. Su Q, Li L, Wang J, et al. Mechanism of programmed cell death factor 4/nuclear factor-κB signaling pathway in porcine coronary micro-embolization-induced cardiac dysfunction. Exp Biol Med (Maywood), 2015, 240(11): 1426-1433.
43. Wang Y, Zhou J, Zhang Y, et al. Delivery of TFPI-2 using SonoVue and adenovirus results in the suppression of thrombosis and arterial re-stenosis. Exp Biol Med (Maywood), 2010, 235(9): 1072-1081.
44. 蘇強. 超聲微泡靶向介導 microRNA-21 調控 PDCD4/NF-κB/TNF-α 通路防治冠狀動脈微栓塞致心肌損傷機制的研究. 廣西醫科大學, 2015.1-20.
45. Chen S, Ding J, Yu C, et al. Reversal of streptozotocin-induced diabetes in rats by gene therapy with betacellulin and pancreatic duodenal homeobox-1. Gene Ther, 2007, 14(14): 1102-1110.
46. Chen S, Shimoda M, Wang MY, et al. Regeneration of pancreatic islets in vivo by ultrasound-targeted gene therapy. Gene Ther, 2010, 17(11): 1411-1420.
47. Chen S, Shimoda M, Chen J, et al. Transient overexpression of cyclin D2/CDK4/GLP1 genes induces proliferation and differentiation of adult pancreatic progenitors and mediates islet regeneration. Cell Cycle, 2012, 11(4): 695-705.
48. Chen S, Shimoda M, Chen J, et al. Ectopic transgenic expression of NKX2.2 induces differentiation of adult pancreatic progenitors and mediates islet regeneration. Cell Cycle, 2012, 11(8): 1544-1553.
49. Chen S, Bastarrachea RA, Roberts BJ, et al. Successful beta cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1. Cell Cycle, 2014, 13(7): 1145-1151.
50. Castle JW, Kent KP, Fan Y, et al. Therapeutic ultrasound: increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids. Atherosclerosis, 2015, 241(1): 92-99.

Previous Article
Research and application progress of mechanical circulatory support devices for univentricular circulation
Next Article
代謝性疾病外科手術方式的發展及演變

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

The status and prospect of ultrasound and microbubble-mediated gene delivery in cardiovascular disease gene therapy

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content