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

Helen Gosnell, Laura M. Kasman, Thrimoorthy Potta, Lucas Vu, Elizabeth Garrett-Mayer, Kaushal Rege, Christina Voelkel-Johnson

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Gene therapy has garnered significant attention as a therapeutic approach for bladder cancer but efficient delivery and gene expression remain major 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.

Original languageEnglish (US)
Pages (from-to)35-43
Number of pages9
JournalJournal of Controlled Release
Volume176
Issue number1
DOIs
StatePublished - Feb 28 2014

Fingerprint

Urinary Bladder Neoplasms
Polymers
Gene Expression
Polyamines
Aminoglycosides
Genetic Therapy
Paromomycin
Neoplasm Genes
Reporter Genes
Adenoviridae
Urinary Bladder
Therapeutics
In Vitro Techniques

Keywords

  • Adenovirus
  • Bladder cancer
  • Cationic polymer
  • Gene delivery
  • Orthotopic

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Polymer-enhanced delivery increases adenoviral gene expression in an orthotopic model of bladder cancer. / Gosnell, Helen; Kasman, Laura M.; Potta, Thrimoorthy; Vu, Lucas; Garrett-Mayer, Elizabeth; Rege, Kaushal; Voelkel-Johnson, Christina.

In: Journal of Controlled Release, Vol. 176, No. 1, 28.02.2014, p. 35-43.

Research output: Contribution to journalArticle

Gosnell, Helen ; Kasman, Laura M. ; Potta, Thrimoorthy ; Vu, Lucas ; Garrett-Mayer, Elizabeth ; Rege, Kaushal ; Voelkel-Johnson, Christina. / Polymer-enhanced delivery increases adenoviral gene expression in an orthotopic model of bladder cancer. In: Journal of Controlled Release. 2014 ; Vol. 176, No. 1. pp. 35-43.
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