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磁性纳米颗粒作为基于肽的DNA递送系统的组成部分用于子宫肌瘤的自杀基因治疗

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

作者信息

Shtykalova Sofia, Egorova Anna, Maretina Marianna, Baranov Vladislav, Kiselev Anton

机构信息

Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia.

出版信息

Bioengineering (Basel). 2022 Mar 8;9(3):112. doi: 10.3390/bioengineering9030112.

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef46/8945779/929738f86171/bioengineering-09-00112-g001.jpg

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