Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo.
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.
Chumakova
Olga V
OV
Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX 77555, USA.
Liopo
Anton V
AV
Andreev
Valery G
VG
Cicenaite
Inga
I
Evers
B Mark
BM
Chakrabarty
Shilla
S
Pappas
Todd C
TC
Esenaliev
Rinat O
RO
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage*; D011094:Polyethyleneimine / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*; D014464:Ultrasonic Therapy / Q000379:methods; D014463:Ultrasonography; D001616:beta-Galactosidase / Q000235:genetics* / Q000378:metabolism
D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011094:Polyethyleneimine; D004247:DNA; D001616:beta-Galactosidase