Delivery of plasmid DNA through intratumoral infusion and electroporation
We investigated DNA transport in the interstitial space and across cell membrane facilitated by intratumoral infusion and in vivo electroporation, respectively. In the study, a rat fibrosarcoma was perfused ex vivo, and apparent hydraulic conductivity (K app ) was quantified under different perfusion conditions. In addition, three plasmid DNA vectors were infused into solid tumors. Immediately after infusion, tumors were treated with or without electric pulses. Gene expression and tumor growth delay were determined at different time points after electroporation. We found that K app was very sensitive to the perfusion pressure, presumably due to perfusion-induced tissue deformation. Treatment of tumors with electric pulse facilitated gene expression in vivo. The growth of tumors treated with plasmid DNA encoding interleukin 12 (IL-12) and electric pulses was slower than those treated with IL-12 or electric pulses alone. These data suggest that gene delivery in solid tumors could be improved significantly through combination of intratumoral infusion and in vivo electroporation.
Yuan, F; Zaharoff, D; Zhang, XY; Lohr, F; Dewhirst, MW; Li, CY
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