Polymer-enhanced delivery increases adenoviral gene expression in an orthotopic model of bladder cancer

被引:21
作者
Gosnell, Helen [1 ]
Kasman, Laura M. [1 ]
Potta, Thrimoorthy [3 ]
Vu, Lucas [3 ]
Garrett-Mayer, Elizabeth [2 ]
Rege, Kaushal [3 ]
Voelkel-Johnson, Christina [1 ]
机构
[1] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA
[2] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA
[3] Arizona State Univ, Sch Engn Matter Transport & Energy, Tempe, AZ 85287 USA
基金
美国国家卫生研究院;
关键词
Gene delivery; Cationic polymer; Adenovirus; Bladder cancer; Orthotopic; RETROVIRUS TRANSDUCTION; RECEPTOR EXPRESSION; IN-VITRO; THERAPY; SYSTEMS; VECTORS; CELLS; INHIBITION; EPITHELIUM; CARCINOMA;
D O I
10.1016/j.jconrel.2013.12.012
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Gene therapy has garnered significant attention as a therapeutic approach for bladder cancer but efficient delivery and gene expression remainmajor hurdles. The goal of this study was to determine if cationic polymers can enhance adenoviral gene expression in cells that are difficult to transduce in vitro and to subsequently investigate lead candidates for their capacity to increase adenoviral gene expression in an orthotopic in vivo model of bladder cancer. In vitro screening of linear polyamine-based and aminoglycoside-based polymer libraries identified several candidates that enhanced adenoviral reporter gene expression in vitro. The polyamine-based polymer NPGDE-1,4 Bis significantly enhanced adenoviral gene expression in the orthotopic model of bladder cancer but unfortunately further use of this polymer was limited by toxicity. In contrast, the aminoglycoside-based polymer paromomycin-BGDE, enhanced adenoviral gene expression within the bladder without adverse events. Our study demonstrates for the first time that cationic polymers can enhance adenoviral gene expression in an orthotopic model of bladder cancer, thereby providing the foundation for future studies to determine therapeutic benefits of polymer-adenovirus combination in bladder cancer gene therapy. (C) 2013 Elsevier B. V. All rights reserved.
引用
收藏
页码:35 / 43
页数:9
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