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

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

doi:10.3390/bioengineering9030112

Sofia Shtykalova, Vladislav Baranov + Show 3 more

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https://doi.org/10.3390/bioengineering9030112

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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.

Highlights

Academic Editors: ÁrpádUterine leiomyomas (ULs) occupy the second place in the structure of gynaecological pathology and are the most common tumor of the female reproductive tract [1]
The UL cells were cultured in AmnioMAX C100 Complete Medium (Thermo Fisher Scientific, Carlsbad, CA, USA) and transfection experiments were held in Dulbecco’s Modified Eagle Media (DMEM)-F12 (Thermo Fisher Scientific) supplemented with 10%
These results demonstrate that the addition of magnetic nanoparticles (MNPs) to the nucleopeptide polyplexes does not influence the nucleopeptide polyplexes density and DNA binding ability of peptide carrier R6p-cRGD

Summary

Introduction

Academic Editors: ÁrpádUterine leiomyomas (ULs) occupy the second place in the structure of gynaecological pathology and are the most common tumor of the female reproductive tract [1]. The frequency of ULs is from 35 to 70% among reproductive-aged women [2]. Despite being benign, these tumors can cause severe symptoms such as excessive uterine bleeding, pelvic pain, menorrhagia, infertility, and pregnancy loss [3]. These tumors can cause severe symptoms such as excessive uterine bleeding, pelvic pain, menorrhagia, infertility, and pregnancy loss [3] These clinical complications affect women’s health and quality of life and are the most common reasons for hysterectomy [4]. Drug treatments, such as the use of GnRH antagonists and aromatase inhibitors, have been developed; hypoestrogenic side-effects, such as bone loss, occur [5]. The absence of metastasis, the precise localization of leiomyoma nodes detected by ultrasound, and the availability of various endoscopic techniques make UL an ideal target for gene therapy in situ

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