Cargando…

DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma

TRAIL (TNF-related apoptosis-inducing ligand) and its derivatives are potentials for anticancer therapy due to the selective induction of apoptosis in tumor cells upon binding to death receptors DR4 or DR5. Previously, we generated a DR5-selective TRAIL mutant variant DR5-B overcoming receptor-depen...

Descripción completa

Detalles Bibliográficos
Autores principales: Yagolovich, Anne V., Isakova, Alina A., Artykov, Artem A., Vorontsova, Yekaterina V., Mazur, Diana V., Antipova, Nadezhda V., Pavlyukov, Marat S., Shakhparonov, Mikhail I., Gileva, Anastasia M., Markvicheva, Elena A., Plotnikova, Ekaterina A., Pankratov, Andrey A., Kirpichnikov, Mikhail P., Gasparian, Marine E., Dolgikh, Dmitry A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604365/
https://www.ncbi.nlm.nih.gov/pubmed/36293545
http://dx.doi.org/10.3390/ijms232012687
_version_ 1784817795669688320
author Yagolovich, Anne V.
Isakova, Alina A.
Artykov, Artem A.
Vorontsova, Yekaterina V.
Mazur, Diana V.
Antipova, Nadezhda V.
Pavlyukov, Marat S.
Shakhparonov, Mikhail I.
Gileva, Anastasia M.
Markvicheva, Elena A.
Plotnikova, Ekaterina A.
Pankratov, Andrey A.
Kirpichnikov, Mikhail P.
Gasparian, Marine E.
Dolgikh, Dmitry A.
author_facet Yagolovich, Anne V.
Isakova, Alina A.
Artykov, Artem A.
Vorontsova, Yekaterina V.
Mazur, Diana V.
Antipova, Nadezhda V.
Pavlyukov, Marat S.
Shakhparonov, Mikhail I.
Gileva, Anastasia M.
Markvicheva, Elena A.
Plotnikova, Ekaterina A.
Pankratov, Andrey A.
Kirpichnikov, Mikhail P.
Gasparian, Marine E.
Dolgikh, Dmitry A.
author_sort Yagolovich, Anne V.
collection PubMed
description TRAIL (TNF-related apoptosis-inducing ligand) and its derivatives are potentials for anticancer therapy due to the selective induction of apoptosis in tumor cells upon binding to death receptors DR4 or DR5. Previously, we generated a DR5-selective TRAIL mutant variant DR5-B overcoming receptor-dependent resistance of tumor cells to TRAIL. In the current study, we improved the antitumor activity of DR5-B by fusion with a tumor-homing iRGD peptide, which is known to enhance the drug penetration into tumor tissues. The obtained bispecific fusion protein DR5-B-iRGD exhibited dual affinity for DR5 and integrin αvβ3 receptors. DR5-B-iRGD penetrated into U-87 tumor spheroids faster than DR5-B and demonstrated an enhanced antitumor effect in human glioblastoma cell lines T98G and U-87, as well as in primary patient-derived glioblastoma neurospheres in vitro. Additionally, DR5-B-iRGD was highly effective in a xenograft mouse model of the U-87 human glioblastoma cell line in vivo. We suggest that DR5-B-iRGD may become a promising candidate for targeted therapy for glioblastoma.
format Online
Article
Text
id pubmed-9604365
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96043652022-10-27 DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma Yagolovich, Anne V. Isakova, Alina A. Artykov, Artem A. Vorontsova, Yekaterina V. Mazur, Diana V. Antipova, Nadezhda V. Pavlyukov, Marat S. Shakhparonov, Mikhail I. Gileva, Anastasia M. Markvicheva, Elena A. Plotnikova, Ekaterina A. Pankratov, Andrey A. Kirpichnikov, Mikhail P. Gasparian, Marine E. Dolgikh, Dmitry A. Int J Mol Sci Article TRAIL (TNF-related apoptosis-inducing ligand) and its derivatives are potentials for anticancer therapy due to the selective induction of apoptosis in tumor cells upon binding to death receptors DR4 or DR5. Previously, we generated a DR5-selective TRAIL mutant variant DR5-B overcoming receptor-dependent resistance of tumor cells to TRAIL. In the current study, we improved the antitumor activity of DR5-B by fusion with a tumor-homing iRGD peptide, which is known to enhance the drug penetration into tumor tissues. The obtained bispecific fusion protein DR5-B-iRGD exhibited dual affinity for DR5 and integrin αvβ3 receptors. DR5-B-iRGD penetrated into U-87 tumor spheroids faster than DR5-B and demonstrated an enhanced antitumor effect in human glioblastoma cell lines T98G and U-87, as well as in primary patient-derived glioblastoma neurospheres in vitro. Additionally, DR5-B-iRGD was highly effective in a xenograft mouse model of the U-87 human glioblastoma cell line in vivo. We suggest that DR5-B-iRGD may become a promising candidate for targeted therapy for glioblastoma. MDPI 2022-10-21 /pmc/articles/PMC9604365/ /pubmed/36293545 http://dx.doi.org/10.3390/ijms232012687 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
Yagolovich, Anne V.
Isakova, Alina A.
Artykov, Artem A.
Vorontsova, Yekaterina V.
Mazur, Diana V.
Antipova, Nadezhda V.
Pavlyukov, Marat S.
Shakhparonov, Mikhail I.
Gileva, Anastasia M.
Markvicheva, Elena A.
Plotnikova, Ekaterina A.
Pankratov, Andrey A.
Kirpichnikov, Mikhail P.
Gasparian, Marine E.
Dolgikh, Dmitry A.
DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma
title DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma
title_full DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma
title_fullStr DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma
title_full_unstemmed DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma
title_short DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma
title_sort dr5-selective trail variant dr5-b functionalized with tumor-penetrating irgd peptide for enhanced antitumor activity against glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604365/
https://www.ncbi.nlm.nih.gov/pubmed/36293545
http://dx.doi.org/10.3390/ijms232012687
work_keys_str_mv AT yagolovichannev dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT isakovaalinaa dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT artykovartema dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT vorontsovayekaterinav dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT mazurdianav dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT antipovanadezhdav dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT pavlyukovmarats dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT shakhparonovmikhaili dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT gilevaanastasiam dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT markvichevaelenaa dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT plotnikovaekaterinaa dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT pankratovandreya dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT kirpichnikovmikhailp dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT gasparianmarinee dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma
AT dolgikhdmitrya dr5selectivetrailvariantdr5bfunctionalizedwithtumorpenetratingirgdpeptideforenhancedantitumoractivityagainstglioblastoma