Delivery of plasmid DNA through intratumoral infusion and electroporation
We investigated DNA transport in the interstitial spaceand across cell membrane facilitated by intratumoral infusionand in vivo electroporation, respectively. In the study, a ratfibrosarcoma was perfused ex vivo, and apparent hydraulicconductivity (Kaap) was quantified under different perfusionconditions. In addition, three plasmid DNA vectors wereinfused into solid tumors. Immediately after infusion, tumorswere treated with or without electric pulses. Gene expressionand tumor growth delay were determined at different timepoints after electroporation. We found that K m was verysensitive to the perfusion pressure, presumably due toperfusion-induced tissue deformation. Treatment of tumorswith electric pulse facilitated gene expression in vivo. Thegrowth of tumors treated with plasmid DNA encodinginterleukin 12 (IL-12) and electric pulses was slower thanthose treated with IL-12 or electric pulses alone. These datasuggest that gene delivery in solid tumors could be improvedsignificantly through combination of intratumoral infusion andin vivo electroporation.
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