Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA.
The possibility of using genes as medicines to treat cancer is limited by the lack of safe and efficacious delivery systems able to deliver therapeutic genes selectively to tumors by intravenous administration. We investigate if the conjugation of the polypropylenimine dendrimer to transferrin, whose receptors are overexpressed on numerous cancers, could result in a selective gene delivery to tumors after intravenous administration, leading to an increased therapeutic efficacy. The objectives of this study are to evaluate the targeting and therapeutic efficacies of a novel transferrin-bearing polypropylenimine dendrimer. The intravenous administration of transferrin-bearing polypropylenimine polyplex resulted in gene expression mainly in the tumors. Consequently, the intravenous administration of the delivery system complexed to a therapeutic DNA led to a rapid and sustained tumor regression over one month, with long-term survival of 100% of the animals (90% complete response, 10% partial response).The treatment was well tolerated by the animals, with no apparent signs of toxicity. Transferrin-bearing polypropylenimine may thus be a promising gene delivery system for cancer therapy.
Koppu
Swati
S
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom.
Oh
Yew Jinn
YJ
Edrada-Ebel
RuAngelie
R
Blatchford
David R
DR
Tetley
Laurence
L
Tate
Rothwelle J
RJ
Dufès
Christine
C
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D050091:Dendrimers / Q000737:chemistry*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005909:Glioblastoma / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011126:Polypropylenes / Q000737:chemistry*; D014162:Transfection; D014168:Transferrin / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D050091:Dendrimers; D011126:Polypropylenes; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha; C443641:poly(propyleneimine); D004247:DNA