Egorova Anna, Shtykalova Sofia, Selutin Alexander, Shved Natalia, Maretina Marianna, Selkov Sergei, Baranov Vladislav, Kiselev Anton
Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya line 3, 199034 Saint-Petersburg, Russia.
Department of Immunology and Intercellular Interactions, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya line 3, 199034 Saint-Petersburg, Russia.
Pharmaceutics. 2021 Feb 2;13(2):202. doi: 10.3390/pharmaceutics13020202.
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.
子宫平滑肌瘤（UL）是女性最常见的良性肿瘤之一，常导致许多生殖并发症。自杀基因疗法被认为是一种有前景的UL治疗方法。在本研究中，我们描述了iRGD配体偶联的富含半胱氨酸的肽载体RGD1-R6，用于将DNA靶向递送至表达αvβ3整合素的原发性UL细胞。研究了DNA/RGD1-R6复合物的物理化学性质、细胞毒性、转染效率和特异性。将编码单纯疱疹病毒1型胸苷激酶的质粒递送至PANC-1胰腺癌细胞和原发性UL细胞，产生了显著的自杀基因治疗效果。随后的更昔洛韦治疗降低了细胞增殖活性，诱导了细胞凋亡并促进了细胞死亡。所得结果使我们得出结论，所开发的RGD1-R6载体可被认为是子宫平滑肌瘤自杀基因治疗的有前景的候选者。
