In vitro evaluation of anti-angiogenesis property of anti-VEGFR2 nanobody-conjugated H40-PEG carrier loaded with methotrexate

Objective(s): In this study, Boltorn® H40-PEG-MTX-anti-VEGFR2 nanobody was fabricated in which nanobody was selected for blocking the receptor, H40 as a nanocarrier for delivery of methotrexate (MTX) to the tumor cells, and polyethylene glycol (PEG) moieties for improving the blood circulation time...

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Main Authors: Seyed Masih Adyani, Hamid Rashidzadeh, Mahdi Behdani, Seyed Jamal Tabatabaei Rezaei, Ali Ramazani
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2022-12-01
Series:Iranian Journal of Basic Medical Sciences
Subjects:
Online Access:https://ijbms.mums.ac.ir/article_21218_94249941c8ac4e5e7cdc9eeb993f2010.pdf
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author Seyed Masih Adyani
Hamid Rashidzadeh
Mahdi Behdani
Seyed Jamal Tabatabaei Rezaei
Ali Ramazani
author_facet Seyed Masih Adyani
Hamid Rashidzadeh
Mahdi Behdani
Seyed Jamal Tabatabaei Rezaei
Ali Ramazani
author_sort Seyed Masih Adyani
collection DOAJ
description Objective(s): In this study, Boltorn® H40-PEG-MTX-anti-VEGFR2 nanobody was fabricated in which nanobody was selected for blocking the receptor, H40 as a nanocarrier for delivery of methotrexate (MTX) to the tumor cells, and polyethylene glycol (PEG) moieties for improving the blood circulation time and safety. Materials and Methods: The synthesis process of the nanosystem has been characterized by different analytical methods. Results: The prepared nanoplatform exhibited high drug loading capacity, excellent colloidal stability, and an average particle size of around 105 nm. MTX was successfully conjugated through ester bonds and its release profile clearly showed that the ester bond is in favor of releasing the drug in acidic pH (5.5). The cytotoxicity of the developed nanoplatform exhibited great anti-cancer activity against MCF7 and KDR293 (cells with overexpressed anti-VEGFR2 NB receptors) cell lines while no deleterious toxicity was observed for nanocarrier against HEK293 normal cells.  Furthermore, both hemolysis and LD50 assay results confirmed the hemocompatibility and biocompatibility of the developed nanoplatform. Conclusion: The most striking result to derive from the data is that the designed nanoplatform could potentially inhibit cell migration and invasion and the anti-angiogenesis properties of the developed nanoplatform may serve as a promising nanosystem to suppress the formation of blood vessels around tumor cells and consequently inhibit tumor progression.
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spelling doaj.art-df819de7170c4639896dbc44f62b53872022-12-25T11:14:14ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742022-12-0125121477148610.22038/ijbms.2022.67038.1470121218In vitro evaluation of anti-angiogenesis property of anti-VEGFR2 nanobody-conjugated H40-PEG carrier loaded with methotrexateSeyed Masih Adyani0Hamid Rashidzadeh1Mahdi Behdani2Seyed Jamal Tabatabaei Rezaei3Ali Ramazani4Pharmaceutical Biomaterials Department, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IranPharmaceutical Biomaterials Department, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IranDepartment of Molecular Medicine, Pasture Institute of Iran, Tehran, IranDepartment of Chemistry, University of Zanjan, Zanjan, IranCancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, IranObjective(s): In this study, Boltorn® H40-PEG-MTX-anti-VEGFR2 nanobody was fabricated in which nanobody was selected for blocking the receptor, H40 as a nanocarrier for delivery of methotrexate (MTX) to the tumor cells, and polyethylene glycol (PEG) moieties for improving the blood circulation time and safety. Materials and Methods: The synthesis process of the nanosystem has been characterized by different analytical methods. Results: The prepared nanoplatform exhibited high drug loading capacity, excellent colloidal stability, and an average particle size of around 105 nm. MTX was successfully conjugated through ester bonds and its release profile clearly showed that the ester bond is in favor of releasing the drug in acidic pH (5.5). The cytotoxicity of the developed nanoplatform exhibited great anti-cancer activity against MCF7 and KDR293 (cells with overexpressed anti-VEGFR2 NB receptors) cell lines while no deleterious toxicity was observed for nanocarrier against HEK293 normal cells.  Furthermore, both hemolysis and LD50 assay results confirmed the hemocompatibility and biocompatibility of the developed nanoplatform. Conclusion: The most striking result to derive from the data is that the designed nanoplatform could potentially inhibit cell migration and invasion and the anti-angiogenesis properties of the developed nanoplatform may serve as a promising nanosystem to suppress the formation of blood vessels around tumor cells and consequently inhibit tumor progression.https://ijbms.mums.ac.ir/article_21218_94249941c8ac4e5e7cdc9eeb993f2010.pdfangiogenesis inhibitorsmethotrexatepolymersingle-domain antibodiesvascular endothelial - growth factor receptor-2
spellingShingle Seyed Masih Adyani
Hamid Rashidzadeh
Mahdi Behdani
Seyed Jamal Tabatabaei Rezaei
Ali Ramazani
In vitro evaluation of anti-angiogenesis property of anti-VEGFR2 nanobody-conjugated H40-PEG carrier loaded with methotrexate
Iranian Journal of Basic Medical Sciences
angiogenesis inhibitors
methotrexate
polymer
single-domain antibodies
vascular endothelial - growth factor receptor-2
title In vitro evaluation of anti-angiogenesis property of anti-VEGFR2 nanobody-conjugated H40-PEG carrier loaded with methotrexate
title_full In vitro evaluation of anti-angiogenesis property of anti-VEGFR2 nanobody-conjugated H40-PEG carrier loaded with methotrexate
title_fullStr In vitro evaluation of anti-angiogenesis property of anti-VEGFR2 nanobody-conjugated H40-PEG carrier loaded with methotrexate
title_full_unstemmed In vitro evaluation of anti-angiogenesis property of anti-VEGFR2 nanobody-conjugated H40-PEG carrier loaded with methotrexate
title_short In vitro evaluation of anti-angiogenesis property of anti-VEGFR2 nanobody-conjugated H40-PEG carrier loaded with methotrexate
title_sort in vitro evaluation of anti angiogenesis property of anti vegfr2 nanobody conjugated h40 peg carrier loaded with methotrexate
topic angiogenesis inhibitors
methotrexate
polymer
single-domain antibodies
vascular endothelial - growth factor receptor-2
url https://ijbms.mums.ac.ir/article_21218_94249941c8ac4e5e7cdc9eeb993f2010.pdf
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