Enhancement of electric field-mediated gene delivery through pretreatment of tumors with a hyperosmotic mannitol solution
| Autor: | Brian Mossop, Fan Yuan, Joshua W. Henshaw |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Electrophoresis
Cancer Research Melanoma Experimental Cytomegalovirus Biology Gene delivery Article Mice 03 medical and health sciences 0302 clinical medicine Luciferases Firefly In vivo Cell Line Tumor medicine Extracellular Animals Mannitol in vivo electrophoresis Promoter Regions Genetic Molecular Biology 030304 developmental biology Mice Inbred BALB C 0303 health sciences Reporter gene Osmotic concentration Electroporation Cell Membrane Gene Transfer Techniques Molecular biology Mice Inbred C57BL electric field-mediated gene delivery interstitial transport 030220 oncology & carcinogenesis Molecular Medicine Female Ex vivo medicine.drug |
| Zdroj: | Cancer gene therapy |
| ISSN: | 1476-5500 0929-1903 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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