Primary cardiomyocyte-targeted bioreducible polymer for efficient gene delivery to the myocardium

被引:59
作者
Nam, Hye Y. [4 ]
McGinn, Arlo [4 ]
Kim, Pyung-Hwan [2 ,3 ]
Kim, Sung W. [4 ]
Bull, David A. [1 ]
机构
[1] Univ Utah, Hlth Sci Ctr, Div Cardiothorac Surg, Sch Med, Salt Lake City, UT 84132 USA
[2] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul, South Korea
[3] Yonsei Univ, Coll Med, Inst Canc Res, Seoul, South Korea
[4] Univ Utah, CCCD, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA
关键词
Cardiomyocyte; siRNA; Fas; PCM; Bioreducible polymer; ENHANCED TRANSFECTION EFFICIENCY; ISCHEMIA/REPERFUSION; POLYPLEXES; EXPRESSION; APOPTOSIS; SELECTION; PEPTIDES; VECTORS; SYSTEMS; AMINE);
D O I
10.1016/j.biomaterials.2010.07.025
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
A cardiomyocyte-targeted Fas siRNA delivery system was developed using primary cardiomyocyte (PCM) specific peptide-modified polymers with high transfection efficiency and low cytotoxicity. Primary cardiomyocyte (PCM) specific peptide, selected by phage display, was conjugated to bioreducible poly (cystamine bisacrylamide-diaminohexane, CBA-DAH) (PCD). The specificity of the PCM-modified polymer to cardiomyocytes was confirmed by competition study with free PCM ligand and by delivery to non-cardiomyocyte NIH 3T3 fibroblasts. The cellular binding and uptake of the PCM-polymer/pDNA polyplex was inhibited by addition of free PCM peptide. The impact of PCM conjugation on cellular uptake and transfection efficiency was greater in H9C2 rat cardiomyocytes than in NIH 3T3 cells. Fas siRNA/PCM-polymer polyplexes exhibited significant Fas gene silencing in rat cardiomyocytes under hypoxic conditions, leading to inhibition of cardiomyocyte apoptosis. These findings demonstrate the utility of the addition of a primary cardiomyocyte (PCM) specific peptide modification to a bioreducible polymer for targeted delivery of Fas siRNA to inhibit cardiomyocyte apoptosis. Published by Elsevier Ltd.
引用
收藏
页码:8081 / 8087
页数:7
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