Use of Cationic Microbubbles Targeted to P-selectin to Improve Ultrasound-mediated Gene Transfection of HVEGF to the Ischemic Myocardium

Overview

Journal J Zhejiang Univ Sci B

Specialties Biology
General Medicine

Date 2018 Sep 5

PMID 30178636

Citations 8

Authors

Wei-Hui Shentu

Cao-Xin Yan

Chun-Mei Liu

Rui-Xiang Qi

Yao Wang

Zhao-Xu Huang

Li-Ming Zhou

Xiang-Dong You

Affiliations

Soon will be listed here.

Abstract

Gene therapies have been applied to the treatment of cardiovascular disease, but their use is limited by the need to deliver them to the right target. We have employed targeted contrast ultrasound-mediated gene transfection (TCUMGT) via ultrasound-targeted microbubble destruction (UTMD) to transfer therapeutic genes to specific anatomic and pathological targets. Phospholipid microbubbles (MBs) with pcDNA-human vascular endothelial growth factor 165 (pcDNA-hVEGF) plasmids targeted to P-selectin (MB+P+VEGFp) were created by conjugating monoclonal antibodies against P-selectin to the lipid shell. These microbubbles were divided into four groups: microbubble only (MB), microbubble+P-selectin (MB+P), microbubble+pcDNA-hVEGF plasmid (MB+VEGFp), and microbubble+ P-selectin+pcDNA-hVEGF plasmid (MB+P+VEGFp). The reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) results showed that the VEGF gene was successfully transfected by TCUMGT and the efficiency is increased with P-selectin targeting moiety. UTMD-mediated delivery of VEGF increased myocardial vascular density and improved cardiac function, and MB+P+VEGFp delivery showed greater improvement than MB+VEGFp. This study drew support from TCUGMT technology and took advantage of targeted ultrasound contrast agent to identify ischemic myocardium, release pcDNA-hVEGF recombinant plasmid, and improve the myocardial microenvironment, so promoting the restoration of myocardial function.

Citing Articles

Experimental Study on the Compatibility and Characteristics of a Dual-Target Microbubble Loaded with Anti-miR-33.

Yuan C, Li Y, Liu L, Tayier B, Yang L, Guan L Int J Nanomedicine. 2021; 16:6265-6280.

PMID: 34539179 PMC: 8445104. DOI: 10.2147/IJN.S324514.

Ultrasound and Microbubbles for Targeted Drug Delivery to the Lung Endothelium in ARDS: Cellular Mechanisms and Therapeutic Opportunities.

Sanwal R, Joshi K, Ditmans M, Tsai S, Lee W Biomedicines. 2021; 9(7).

PMID: 34356867 PMC: 8301318. DOI: 10.3390/biomedicines9070803.

Ultrasonic microbubble VEGF gene delivery improves angiogenesis of senescent endothelial progenitor cells.

Lee Y, Wu Y, Lee H, Wang H, Chang C, Tien T Sci Rep. 2021; 11(1):13449.

PMID: 34188086 PMC: 8242093. DOI: 10.1038/s41598-021-92754-3.

Ultrasonic irradiation and SonoVue microbubbles-mediated RNA interference targeting PRR11 inhibits breast cancer cells proliferation and metastasis, but promotes apoptosis.

Luo H, Li J, Lin Q, Xiao X, Shi Y, Ye X Biosci Rep. 2020; 40(11).

PMID: 33057583 PMC: 7607193. DOI: 10.1042/BSR20201854.

Effects of leptin-modified human placenta-derived mesenchymal stem cells on angiogenic potential and peripheral inflammation of human umbilical vein endothelial cells (HUVECs) after X-ray radiation.

Chen S, Wang Q, Han B, Wu J, Liu D, Zou J J Zhejiang Univ Sci B. 2020; 21(4):327-340.

PMID: 32253842 PMC: 7183445. DOI: 10.1631/jzus.B1900598.

References

Douvaras P, Antonatos D, Kekou K, Patsilinakos S, Chouliaras G, Christou A . Association of VEGF gene polymorphisms with the development of heart failure in patients after myocardial infarction. Cardiology. 2009; 114(1):11-8. DOI: 10.1159/000210189. View

Kelly S, Bombardieri M, Humby F, Ng N, Marrelli A, Riahi S . Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study. Arthritis Res Ther. 2015; 17:58. PMC: 4476089. DOI: 10.1186/s13075-015-0567-8. View

Gerhardt H . VEGF and endothelial guidance in angiogenic sprouting. Organogenesis. 2009; 4(4):241-6. PMC: 2634329. DOI: 10.4161/org.4.4.7414. View

Yu Q, Fang W, Zhu N, Zheng X, Na R, Liu B . Beneficial effects of intramyocardial mesenchymal stem cells and VEGF165 plasmid injection in rats with furazolidone induced dilated cardiomyopathy. J Cell Mol Med. 2015; 19(8):1868-76. PMC: 4549037. DOI: 10.1111/jcmm.12558. View

Sirsi S, Borden M . Advances in ultrasound mediated gene therapy using microbubble contrast agents. Theranostics. 2013; 2(12):1208-22. PMC: 3563148. DOI: 10.7150/thno.4306. View

Zhao Z, Corvera J, Halkos M, Kerendi F, Wang N, Guyton R . Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2003; 285(2):H579-88. DOI: 10.1152/ajpheart.01064.2002. View

St John Sutton M, Pfeffer M, Moye L, Plappert T, Rouleau J, Lamas G . Cardiovascular death and left ventricular remodeling two years after myocardial infarction: baseline predictors and impact of long-term use of captopril: information from the Survival and Ventricular Enlargement (SAVE) trial. Circulation. 1997; 96(10):3294-9. DOI: 10.1161/01.cir.96.10.3294. View

Ferrante E, Pickard J, Rychak J, Klibanov A, Ley K . Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow. J Control Release. 2009; 140(2):100-7. PMC: 2783796. DOI: 10.1016/j.jconrel.2009.08.001. View

Takalkar A, Klibanov A, Rychak J, Lindner J, Ley K . Binding and detachment dynamics of microbubbles targeted to P-selectin under controlled shear flow. J Control Release. 2004; 96(3):473-82. DOI: 10.1016/j.jconrel.2004.03.002. View

10.

Lindner J, Song J, Christiansen J, Klibanov A, Xu F, Ley K . Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin. Circulation. 2001; 104(17):2107-12. DOI: 10.1161/hc4201.097061. View

11.

Liu J, Zhang P, Liu P, Zhao Y, Gao S, Tan K . Endothelial adhesion of targeted microbubbles in both small and great vessels using ultrasound radiation force. Mol Imaging. 2012; 11(1):58-66. View

12.

Yau T, Fung K, Weisel R, Fujii T, Mickle D, Li R . Enhanced myocardial angiogenesis by gene transfer with transplanted cells. Circulation. 2001; 104(12 Suppl 1):I218-22. DOI: 10.1161/hc37t1.094896. View

13.

Bekeredjian R, Grayburn P, Shohet R . Use of ultrasound contrast agents for gene or drug delivery in cardiovascular medicine. J Am Coll Cardiol. 2005; 45(3):329-35. DOI: 10.1016/j.jacc.2004.08.067. View

14.

Christiansen J, French B, Klibanov A, Kaul S, Lindner J . Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles. Ultrasound Med Biol. 2003; 29(12):1759-67. DOI: 10.1016/s0301-5629(03)00976-1. View

15.

Hoeben A, Landuyt B, Highley M, Wildiers H, van Oosterom A, De Bruijn E . Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004; 56(4):549-80. DOI: 10.1124/pr.56.4.3. View

16.

Hu D, Liu X, Song W, Wang J . Roles of SIRT3 in heart failure: from bench to bedside. J Zhejiang Univ Sci B. 2016; 17(11):821-830. PMC: 5120224. DOI: 10.1631/jzus.B1600253. View

17.

Fujii H, Li S, Wu J, Miyagi Y, Yau T, Rakowski H . 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):2075-84. DOI: 10.1093/eurheartj/ehq475. View

18.

Unger E, Porter T, Lindner J, Grayburn P . Cardiovascular drug delivery with ultrasound and microbubbles. Adv Drug Deliv Rev. 2014; 72:110-26. DOI: 10.1016/j.addr.2014.01.012. View

19.

Xie A, Belcik T, Qi Y, Morgan T, Champaneri S, Taylor S . Ultrasound-mediated vascular gene transfection by cavitation of endothelial-targeted cationic microbubbles. JACC Cardiovasc Imaging. 2012; 5(12):1253-62. PMC: 3682923. DOI: 10.1016/j.jcmg.2012.05.017. View

20.

Sun L, Huang C, Wu J, Chen K, Li S, Weisel R . The use of cationic microbubbles to improve ultrasound-targeted gene delivery to the ischemic myocardium. Biomaterials. 2012; 34(8):2107-16. DOI: 10.1016/j.biomaterials.2012.11.041. View