Abstract:
:Electro-gene-therapy is a promising technique for cancer treatment. However, knowledge about mechanism of gene transfer with electric field in tumor is limited. Whereas in vitro electrotransfection is efficient, gene expression in tumoral cells in vivo is weak. To determine reasons for this difference and unravel gene transfer mechanisms, we propose to use multicellular tumor spheroid as a tridimensional model ex vivo. Comparison of efficiency between cell in suspension and cells in spheroid allow highlighting fundamental differences. For classical electrical conditions (consisting in 10 pulses of 500V/cm, 5ms, 1Hz), suspension cells present a transfection rate of 23.75%±2.450 SEM. In the same conditions on spheroid, although plasmid DNA coding GFP interact with half of electrically permeabilized cells, less than 1% of cells are expressing the transgene. First answers to in vivo electrotransfection failure are given: cell mortality due to electric field is responsible of this low transfection rate, as tridimensional and multicellular structure that prevents DNA passage. These results show that spheroid is reproducing in vivo situation. Validation of spheroid as a relevant model for electrotransfection study opens ex vivo optimization possibility before in vivo assay.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Chopinet L,Wasungu L,Rols MPdoi
10.1016/j.ijpharm.2011.04.054subject
Has Abstractpub_date
2012-02-14 00:00:00pages
7-15issue
1eissn
0378-5173issn
1873-3476pii
S0378-5173(11)00381-4journal_volume
423pub_type
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