Magnetic Nanoparticles as a Component of Peptide-Based DNA Delivery System for Suicide Gene Therapy of Uterine Leiomyoma

Abstract

Suicidegene therapy is considered a promising approach for the treatment of uterine leiomyoma (UL), a benign tumor in women characterized by precise localization. In this study, we investigate the efficiency of αvβ3 integrin-targeted arginine-rich peptide carrier R6p-cRGD electrostatically bound to magnetic nanoparticles (MNPs) for targeted DNA delivery into the UL cells. The physico–chemical and cytotoxic properties, transfection efficiency, and specificity of R6p-cRGD/DNA/MNPs polyplexes were evaluated. The addition of MNPs resulted in a decrease in the time needed for successful transfection with simultaneous increase in efficiency. We revealed a therapeutic effect on primary UL cells after delivery of plasmid encoding the herpes simplex virus type 1 (HSV-1) thymidine kinase gene. Treatment with ganciclovir resulted in 20% efficiency of suicide gene therapy in UL cells transfected with the pPTK-1 plasmid. Based on these results, we conclude that the use of cationic peptide carriers with MNPs can be promising for the development of modular non-viral carriers for suicide gene delivery to UL cells.

Keywords

• DNA delivery
• peptide-based carriers
• gene therapy
• magnetic nanoparticles
• thymidine kinase
• uterine leiomyoma