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

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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.

In: International Journal of Molecular Sciences, Vol. 23, No. 3, 1164, 21.01.2022.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{79623f55068c450e86447a6f8ed37901,

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

abstract = "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.",

keywords = "DNA delivery, Gene therapy, Integrins, Peptide-based carriers, Polycondensation, Thymidine kinase, Uterine fi-broids, THYMIDINE KINASE GENE, thymidine kinase, LEIOMYOMA, TRANSFECTION EFFICIENCY, gene therapy, peptide-based carriers, POTENTIAL BARRIER, DNA DELIVERY, polycondensation, IN-VITRO, integrins, THERAPY, PLASMID DNA, uterine fibroids, VECTORS, PENETRATING PEPTIDES",

author = "Anna Egorova and Sofia Shtykalova and Marianna Maretina and Alexander Selutin and Natalia Shved and Dmitriy Deviatkin and Sergey Selkov and Vladislav Baranov and Anton Kiselev",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = jan,

day = "21",

doi = "10.3390/ijms23031164",

language = "English",

volume = "23",

journal = "International Journal of Molecular Sciences",

issn = "1422-0067",

publisher = "MDPI AG",

number = "3",

}

RIS

TY - JOUR

T1 - Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells

AU - Egorova, Anna

AU - Shtykalova, Sofia

AU - Maretina, Marianna

AU - Selutin, Alexander

AU - Shved, Natalia

AU - Deviatkin, Dmitriy

AU - Selkov, Sergey

AU - Baranov, Vladislav

AU - Kiselev, Anton

PY - 2022/1/21

Y1 - 2022/1/21

N2 - 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.

AB - 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.

KW - DNA delivery

KW - Gene therapy

KW - Integrins

KW - Peptide-based carriers

KW - Polycondensation

KW - Thymidine kinase

KW - Uterine fi-broids

KW - THYMIDINE KINASE GENE

KW - thymidine kinase

KW - LEIOMYOMA

KW - TRANSFECTION EFFICIENCY

KW - gene therapy

KW - peptide-based carriers

KW - POTENTIAL BARRIER

KW - DNA DELIVERY

KW - polycondensation

KW - IN-VITRO

KW - integrins

KW - THERAPY

KW - PLASMID DNA

KW - uterine fibroids

KW - VECTORS

KW - PENETRATING PEPTIDES

UR - http://www.scopus.com/inward/record.url?scp=85124679423&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/3d04124e-97e6-37fe-badd-b991a00b83af/

U2 - 10.3390/ijms23031164

DO - 10.3390/ijms23031164

M3 - Article

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 3

M1 - 1164

ER -

ID: 92159731