期刊
JOURNAL OF CONTROLLED RELEASE
卷 170, 期 3, 页码 437-444出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2013.06.005
关键词
Ultrasound-targeted microbubble destruction; Cell-permeable peptide; Gene transfection; Myocardial infarction
资金
- National Natural Science Foundation of China [81130025, 81000621, 81227801, 81161120548]
- Program of Education Ministry New Teacher Foundation of China [20105503120008]
- Program of Chongqing university scientific innovation team
- Program of National Key Basic Research and Development of China [2011CB707900]
Cell-permeable peptides (CPPs) and ultrasound-targeted microbubble destruction (UTMD) have tremendous potential for gene delivery. However, their applications are limited due to nonspecificity of CPPs and low transfection efficiency of UTMD. Here, we developed a 'smart' gene delivery system by encapsulating TAT peptide (TATp) and hepatocyte growth factor (HGF) gene within lipid microbubbles, in which TATp was protected from being enzymatically cleaved and HGF gene was protected from degradation. This new strategy had synergistic effects of UTMD and TATp on gene transfection. We investigated the efficacy and safety of HGF gene transfection mediated by the combination of UTMD and TATp in vitro and in vivo. The results from MTT assay and flow cytometry analyses indicated that the combination of UTMD and TATp could enhance HGF gene expression in HUVECs without any significant side effect on cell viability. In rat myocardial infarction models, we demonstrated that the protein and mRNA expressions of HGF in myocardium caused by the combination of UTMD and TATp were the highest. Histopathological findings demonstrated that the combination of UTMD and TATp enhanced myocardial microvasculature and ameliorated myocardial fibrosis. In conclusion, the combination of UTMD and TATp might be a safe and efficient technique for gene delivery. (C) 2013 Elsevier B. V. All rights reserved.
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