Journal
JOURNAL OF CONTROLLED RELEASE
Volume 176, Issue -, Pages 35-43Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2013.12.012
Keywords
Gene delivery; Cationic polymer; Adenovirus; Bladder cancer; Orthotopic
Funding
- National Institutes of Health from the National Cancer Institute [R21 CA143505]
- National Institutes of Health from the National Institute of General Medical Sciences [R01GM093229]
- Hollings Cancer Center from the National Center for Research Resources
- Office of the Direction of National Institute of Health [C06 RR015455]
- National Cancer Institute [P30 CA138313]
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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.
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