Shtykalova Sofia, Egorova Anna, Maretina Marianna, 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.
Bioengineering (Basel). 2022 Mar 8;9(3):112. doi: 10.3390/bioengineering9030112.
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.
自杀基因疗法被认为是治疗子宫平滑肌瘤（UL）的一种有前景的方法，子宫平滑肌瘤是一种女性良性肿瘤，具有精确定位的特征。在本研究中，我们研究了与磁性纳米颗粒（MNP）静电结合的αvβ3整合素靶向富精氨酸肽载体R6p-cRGD将靶向DNA递送至UL细胞的效率。评估了R6p-cRGD/DNA/MNP复合物的物理化学和细胞毒性特性、转染效率及特异性。添加MNP导致成功转染所需时间减少，同时效率提高。我们揭示了在递送编码单纯疱疹病毒1型（HSV-1）胸苷激酶基因的质粒后对原代UL细胞的治疗效果。用更昔洛韦治疗导致在用pPTK-1质粒转染的UL细胞中自杀基因疗法的效率达到20%。基于这些结果，我们得出结论，阳离子肽载体与MNP的联合使用对于开发用于将自杀基因递送至UL细胞的模块化非病毒载体可能具有前景。
