Enhancement of electric field-mediated gene delivery through pretreatment of tumors with a hyperosmotic mannitol solution.

Published

Journal Article

Pulsed electric fields can enhance interstitial transport of plasmid DNA (pDNA) in solid tumors. However, the extent of enhancement is still limited. To this end, the effects of cellular resistance to electric field-mediated gene delivery were investigated. The investigation used two tumor cell lines (4T1 (a murine mammary carcinoma) and B16.F10 (a metastatic subline of B16 murine melanoma)) either in suspensions or implanted in two in vivo models (dorsal skin-fold chamber (DSC) and hind leg). The volume fraction of cells was altered by pretreatment with a hyperosmotic mannitol solution (1 M). It was observed that the pretreatment reduced the volumes of 4T1 and B16.F10 cells, suspended in an agarose gel, by 50 and 46%, respectively, over a 20-min period, but did not cause significant changes ex vivo in volumes of hind-leg tumor tissues grown from the same cells in mice. The mannitol pretreatment in vivo improved electric field-mediated gene delivery in the hind-leg tumor models, in terms of reporter gene expression, but resulted in minimal enhancement in pDNA electrophoresis over a few microns distance in the DSC tumor models. These data demonstrated that hyperosmotic mannitol solution could effectively improve electric field-mediated gene delivery around individual cells in vivo by increasing the extracellular space.

Full Text

Duke Authors

Cited Authors

  • Henshaw, J; Mossop, B; Yuan, F

Published Date

  • January 2011

Published In

Volume / Issue

  • 18 / 1

Start / End Page

  • 26 - 33

PubMed ID

  • 20847751

Pubmed Central ID

  • 20847751

Electronic International Standard Serial Number (EISSN)

  • 1476-5500

International Standard Serial Number (ISSN)

  • 0929-1903

Digital Object Identifier (DOI)

  • 10.1038/cgt.2010.51

Language

  • eng