Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo
- Authors: Chumakova, O. V., Liopo, A. V., Andreev, V. G., Cicenaite, I., Evers, B. M., Chakrabarty, S., Pappas, T. C., Esenaliev, R. O.
- Year: 2008
- Journal: Cancer Lett 261 215-25
- Applications: in vivo / DNA / in vivo-jetPEI
IV delivery of nanopaticles followed by ultrasound treatment to target tumors.
50 µg DNA + 10 µl in vivo-jetPEI in a final volume of 200 µl of 5% glucose + 100 cµl of PLGA. Immediately after injection, the tumors were irradiated by ultrasound.
The goal of this study was to enhance gene delivery and tumor cell transfection in vivo by using a combination of ultrasonication with complex nanoparticles consisting of two types of nanoparticles: PEI/DNA beta-gal plasmid with highly positive zeta-potential and air-filled poly (lactic-co-glycolic acid) (PLGA) particles (with negative zeta-potential) manufactured in our laboratory. The PLGA/PEI/DNA nanoparticles were a colloid with positive zeta-potential and injected i.v. in nude mice with DU145 human prostate tumors. We found that the combination of PLGA/PEI/DNA nanoparticles with ultrasonication substantially enhanced tumor cell transfection in vivo. The overexpression of beta-gal gene was evaluated histochemically and by Western blot analysis. At least an 8-fold increase of the cell transfection efficacy was obtained in irradiated tumors compared to non-irradiated controls, while little to no cell death was produced by ultrasonication.