期刊
JOURNAL OF CONTROLLED RELEASE
卷 138, 期 2, 页码 168-176出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2009.05.023
关键词
Temperature-responsive amphiphilic polymer; Local gene transfer; Angiogenesis; Myocardial infarction
资金
- Ministry of Science Technology [M10641450001-06N4145-00110, M10711060001-08M1106-00110]
- Korea Healthcare technology RD Project
- Ministry for Health, Welfare and Family Affairs, Republic of Korea [A084869]
- Korea-Japan joint Research Project [F01-2008-000-10004-0]
- Korea Health Promotion Institute [A084869] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Thermo-responsive hydrogel-mediated gene transfer may be preferred for the muscle, because the release of DNA into the surrounding tissue can be controlled by the 3-dimensional structure of the hydrogel. Such a system for the controlled release of a therapeutic gene may extend the duration of gene expression. Here, a thermo-responsive, biodegradable polymeric hydrogel was synthesized for local gene transfer in the heart. Initially, the luciferase gene was delivered into mouse heart. The intensity of gene expression assessed by optical imaging was closely correlated with the expressed protein concentration measured by luciferase assay in homogenized heart. Polymeric hydrogel-based gene transfer enhanced gene expression up to 4 fold, compared with naked plasmid, and displayed 2 bi-modal expression profiles with peaks at 2 days and around 25 days after local injection. Histological analyses showed that gene expression was initially highest in the myocardium, whereas lower and longer expression was seen mainly in fibrotic or inflammatory cells that infiltrated the injury site during injection. Next, a rat myocardial infarction model was made for 1 week, and human vascular endothelial growth factor (hVEGF) plasmid was injected into the infarct area with an amphiphilic thermo-responsive polymer. Enhanced and sustained hVEGF expression in the infarct region mediated by amphiphilic thermo-responsive polymer increased capillary density and larger vessel formation, thus enabling effective angiogenesis. (C) 2009 Elsevier B.V. All rights reserved.
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