Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma

Abstract

Uterine leiomyoma (UL) is one of the most common benign tumors in women that often leads to many reproductive complications. Suicide genetherapy was suggested as a promising approach for UL treatment. In the present study, we describe iRGD ligand-conjugated cysteine-rich peptide carrier RGD1-R6 for targeted DNA delivery to αvβ3 integrin-expressing primary UL cells. The physico-chemical properties, cytotoxicity, transfection efficiency and specificity of DNA/RGD1-R6 polyplexes were investigated. TheHSV-1thymidine kinase encoding plasmid delivery to PANC-1pancreatic carcinoma cells and primary UL cells resulted in significant suicide gene therapy effects. Subsequent ganciclovir treatment decreased cells proliferative activity, induced of apoptosis and promoted cells death.The obtained results allow us to concludethatthe developed RGD1-R6 carrier can be considered a promising candidate for suicide gene therapy of uterine leiomyoma.

Keywords

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