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

被引:10
作者
Egorova, Anna [1 ]
Shtykalova, Sofia [1 ]
Selutin, Alexander [2 ]
Shved, Natalia [1 ]
Maretina, Marianna [1 ]
Selkov, Sergei [2 ]
Baranov, Vladislav [1 ]
Kiselev, Anton [1 ]
机构
[1] DO Ott Res Inst Obstet Gynecol & Reproductol, Dept Genom Med, Mendeleevskaya Line 3, St Petersburg 199034, Russia
[2] DO Ott Res Inst Obstet Gynecol & Reproductol, Dept Immunol & Intercellular Interact, Mendeleevskaya Line 3, St Petersburg 199034, Russia
基金
俄罗斯科学基金会;
关键词
DNA delivery; peptide-based carriers; gene therapy; thymidine kinase; uterine leiomyoma; integrins; iRGD; pancreatic carcinoma;
D O I
10.3390/pharmaceutics13020202
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 alpha v beta 3 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.
引用
收藏
页码:1 / 27
页数:25
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