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Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells

Suicide gene therapy was suggested as a possible strategy for the treatment of uterine fibroids (UFs), which are the most common benign tumors inwomen of reproductive age. For successful suicide gene therapy, DNAtherapeutics should be specifically delivered to UF cells. Peptide carriers are promisin...

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Autores principales: Egorova, Anna, Shtykalova, Sofia, Maretina, Marianna, Selutin, Alexander, Shved, Natalia, Deviatkin, Dmitriy, Selkov, Sergey, Baranov, Vladislav, Kiselev, Anton
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835468/
https://www.ncbi.nlm.nih.gov/pubmed/35163086
http://dx.doi.org/10.3390/ijms23031164
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author Egorova, Anna
Shtykalova, Sofia
Maretina, Marianna
Selutin, Alexander
Shved, Natalia
Deviatkin, Dmitriy
Selkov, Sergey
Baranov, Vladislav
Kiselev, Anton
author_facet Egorova, Anna
Shtykalova, Sofia
Maretina, Marianna
Selutin, Alexander
Shved, Natalia
Deviatkin, Dmitriy
Selkov, Sergey
Baranov, Vladislav
Kiselev, Anton
author_sort Egorova, Anna
collection PubMed
description Suicide gene therapy was suggested as a possible strategy for the treatment of uterine fibroids (UFs), which are the most common benign tumors inwomen of reproductive age. For successful suicide gene therapy, DNAtherapeutics should be specifically delivered to UF cells. Peptide carriers are promising non-viral gene delivery systems that can be easily modified with ligands and other biomolecules to overcome DNA transfer barriers. Here we designed polycondensed peptide carriers modified with a cyclic RGD moiety for targeted DNA delivery to UF cells. Molecular weights of the resultant polymers were determined, and inclusion of the ligand was confirmed by MALDI-TOF. The physicochemical properties of the polyplexes, as well as cellular DNA transport, toxicity, and transfection efficiency were studied, and the specificity of αvβ3 integrin-expressing cell transfection was proved. The modification with the ligand resulted in a three-fold increase of transfection efficiency. Modeling of the suicide gene therapy by transferring the HSV-TK suicide gene to primary cells obtained from myomatous nodes of uterine leiomyoma patients was carried out. We observed up to a 2.3-fold decrease in proliferative activity after ganciclovir treatment of the transfected cells. Pro- and anti-apoptotic gene expression analysis confirmed our findings that the developed polyplexes stimulate UF cell death in a suicide-specific manner.
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spelling pubmed-88354682022-02-12 Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells Egorova, Anna Shtykalova, Sofia Maretina, Marianna Selutin, Alexander Shved, Natalia Deviatkin, Dmitriy Selkov, Sergey Baranov, Vladislav Kiselev, Anton Int J Mol Sci Article Suicide gene therapy was suggested as a possible strategy for the treatment of uterine fibroids (UFs), which are the most common benign tumors inwomen of reproductive age. For successful suicide gene therapy, DNAtherapeutics should be specifically delivered to UF cells. Peptide carriers are promising non-viral gene delivery systems that can be easily modified with ligands and other biomolecules to overcome DNA transfer barriers. Here we designed polycondensed peptide carriers modified with a cyclic RGD moiety for targeted DNA delivery to UF cells. Molecular weights of the resultant polymers were determined, and inclusion of the ligand was confirmed by MALDI-TOF. The physicochemical properties of the polyplexes, as well as cellular DNA transport, toxicity, and transfection efficiency were studied, and the specificity of αvβ3 integrin-expressing cell transfection was proved. The modification with the ligand resulted in a three-fold increase of transfection efficiency. Modeling of the suicide gene therapy by transferring the HSV-TK suicide gene to primary cells obtained from myomatous nodes of uterine leiomyoma patients was carried out. We observed up to a 2.3-fold decrease in proliferative activity after ganciclovir treatment of the transfected cells. Pro- and anti-apoptotic gene expression analysis confirmed our findings that the developed polyplexes stimulate UF cell death in a suicide-specific manner. MDPI 2022-01-21 /pmc/articles/PMC8835468/ /pubmed/35163086 http://dx.doi.org/10.3390/ijms23031164 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Egorova, Anna
Shtykalova, Sofia
Maretina, Marianna
Selutin, Alexander
Shved, Natalia
Deviatkin, Dmitriy
Selkov, Sergey
Baranov, Vladislav
Kiselev, Anton
Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells
title Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells
title_full Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells
title_fullStr Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells
title_full_unstemmed Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells
title_short Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells
title_sort polycondensed peptide carriers modified with cyclic rgd ligand for targeted suicide gene delivery to uterine fibroid cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835468/
https://www.ncbi.nlm.nih.gov/pubmed/35163086
http://dx.doi.org/10.3390/ijms23031164
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