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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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 |
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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 |
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