Use of cationic microbubbles targeted to P-selectin to improve ultrasound-mediated gene transfection of hVEGF165 to the ischemic myocardium

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...

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Bibliographic Details
Published in:Journal of Zhejiang University. B. Science 2018-09, Vol.19 (9), p.699-707
Main Authors: Shentu, Wei-hui, Yan, Cao-xin, Liu, Chun-mei, Qi, Rui-xiang, Wang, Yao, Huang, Zhao-xu, Zhou, Li-ming, You, Xiang-dong
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
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Summary: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 3.1 -human vascular endothelial growth factor 165 (pcDNA 3.1 -hVEGF 165 ) 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 3.1 -hVEGF 165 plasmid (MB+VEGFp), and microbubble+ P-selectin+pcDNA 3.1 -hVEGF 165 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 3.1 -hVEGF 165 recombinant plasmid, and improve the myocardial microenvironment, so promoting the restoration of myocardial function.
ISSN:1673-1581
1862-1783
DOI:10.1631/jzus.B1700298