Antitumoral activity of transferrin-lipoplexes carrying the IL-12 gene in the treatment of colon cancer

• Published in: Journal of drug targeting 2006-09, Vol.14 (8), p.527-535
• Main Authors: Tros De Ilarduya, Conchita, Buñuales, Maria, Qian, Cheng, Düzgüne, Nejat
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; cancer gene therapy; Cationic liposomes; Cations; Cells, Cultured; Cholesterol - chemistry; colon carcinoma; Colonic Neoplasms - therapy; Disease Models, Animal; Fatty Acids, Monounsaturated - chemistry; Female; Gene Expression Regulation; Gene Transfer Techniques; General pharmacology; Genetic Therapy - methods; Interferon-gamma - blood; interleukin 12; Interleukin-12 - blood; Interleukin-12 - genetics; Interleukin-12 - therapeutic use; Medical sciences; Mice; Mice, Inbred BALB C; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasmids - administration & dosage; Quaternary Ammonium Compounds - chemistry; Survival Rate; transferrin; Transferrin - administration & dosage
• ISSN: 1061-186X; 1029-2330
• DOI: 10.1080/10611860600825282

The present study aimed to establish an efficient targeted nonviral strategy for IL-12 gene transfer in colon carcinoma in vivo employing transferrin (Tf)-lipoplexes. Complexes for in vitro experiments were prepared at a 5/1(+/ − ) (lipid/DNA) charge ratio, with the ligand Tf (32 (μg/(μg DNA). Complexes for in vivo experiments contained 144 mM of total lipid (DOTAP/Chol), 60 (μg of pCMVLuc or pCMVIL-12 and 32 (μg of Tf-lipoplexes per microgram of plasmid. For intratumoral studies, CT26 (5 × 105 cells) in 50 μl of PBS were inoculated subcutaneously into the back of the mouse. Treatments began when tumor sizes reached 5-6 mm in diameter. Complexes were injected by a single intratumoral injection in a volume of 50 μl. Our in vitro results indicate that Tf-lipoplexes always mediate higher gene expression in colon (CT26) tumor cells, compared to plain-lipoplexes (without ligand) or naked plasmid. At the same time, CT26 tumor-bearing animals treated with Tf-lipoplexes containing the therapeutic gene IL-12, showed tumor growth inhibition, leading to a complete tumor regression in 75% of the treated mice (p < 0.001), without signs of recurrence. High levels of IL-12 and IFN-γ were detected in the sera of treated mice. Mice survival also improved considerably by treatment with this system, with a survival rate of 88%, at 23 days post-administration. In summary, in this study we have developed an efficient, targeted cationic lipid-based system for the treatment of colon tumors. The vector has the advantages of ease of preparation and economy, in comparison with commercial transfection reagents, as well as, the possibility of a large scale production.