Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors

Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors

Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Yaroslav Y Marchenko,3 Anatolii V Dobrodumov,4 Anastasiya L Mikhrina,5 Marina G Martynova,1 Olga A Bystrova,1 Igor V Yakovenko,2 Alexander M Ischenko31Institute of Cytology of the Russian Academy of Sciences (RAS), 2AL Polenov Russian Sc...

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Autores principales: Shevtsov MA, Nikolaev BP, Yakovleva LY, Marchenko YY, Dobrodumov AV, Mikhrina AL, Martynova MG, Bystrova OA, Yakovenko IV, Ischenko AM
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2014
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/396a15a4b8584d33842f4a411a186f78
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spelling oai:doaj.org-article:396a15a4b8584d33842f4a411a186f782021-12-02T02:36:44ZSuperparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors1178-2013https://doaj.org/article/396a15a4b8584d33842f4a411a186f782014-01-01T00:00:00Zhttp://www.dovepress.com/superparamagnetic-iron-oxide-nanoparticles-conjugated-with-epidermal-g-a15420https://doaj.org/toc/1178-2013 Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Yaroslav Y Marchenko,3 Anatolii V Dobrodumov,4 Anastasiya L Mikhrina,5 Marina G Martynova,1 Olga A Bystrova,1 Igor V Yakovenko,2 Alexander M Ischenko31Institute of Cytology of the Russian Academy of Sciences (RAS), 2AL Polenov Russian Scientific Research Institute of Neurosurgery, 3Research Institute of Highly Pure Biopreparations, 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), 5IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS), St Petersburg, RussiaAbstract: Superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with recombinant human epidermal growth factor (SPION–EGF) were studied as a potential agent for magnetic resonance imaging contrast enhancement of malignant brain tumors. Synthesized conjugates were characterized by transmission electron microscopy, dynamic light scattering, and nuclear magnetic resonance relaxometry. The interaction of SPION–EGF conjugates with cells was analyzed in a C6 glioma cell culture. The distribution of the nanoparticles and their accumulation in tumors were assessed by magnetic resonance imaging in an orthotopic model of C6 gliomas. SPION–EGF nanosuspensions had the properties of a negative contrast agent with high coefficients of relaxation efficiency. In vitro studies of SPION–EGF nanoparticles showed high intracellular incorporation and the absence of a toxic influence on C6 cell viability and proliferation. Intravenous administration of SPION–EGF conjugates in animals provided receptor-mediated targeted delivery across the blood–brain barrier and tumor retention of the nanoparticles; this was more efficient than with unconjugated SPIONs. The accumulation of conjugates in the glioma was revealed as hypotensive zones on T2-weighted images with a twofold reduction in T2 relaxation time in comparison to unconjugated SPIONs (P<0.001). SPION–EGF conjugates provide targeted delivery and efficient magnetic resonance contrast enhancement of EGFR-overexpressing C6 gliomas.Keywords: brain tumor, C6 glioma, magnetic nanoparticles, EGFR, epidermal growth factor, MRI contrast agent, SPIONShevtsov MANikolaev BPYakovleva LYMarchenko YYDobrodumov AVMikhrina ALMartynova MGBystrova OAYakovenko IVIschenko AMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 273-287 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Shevtsov MA
Nikolaev BP
Yakovleva LY
Marchenko YY
Dobrodumov AV
Mikhrina AL
Martynova MG
Bystrova OA
Yakovenko IV
Ischenko AM
Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors
description Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Yaroslav Y Marchenko,3 Anatolii V Dobrodumov,4 Anastasiya L Mikhrina,5 Marina G Martynova,1 Olga A Bystrova,1 Igor V Yakovenko,2 Alexander M Ischenko31Institute of Cytology of the Russian Academy of Sciences (RAS), 2AL Polenov Russian Scientific Research Institute of Neurosurgery, 3Research Institute of Highly Pure Biopreparations, 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), 5IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS), St Petersburg, RussiaAbstract: Superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with recombinant human epidermal growth factor (SPION–EGF) were studied as a potential agent for magnetic resonance imaging contrast enhancement of malignant brain tumors. Synthesized conjugates were characterized by transmission electron microscopy, dynamic light scattering, and nuclear magnetic resonance relaxometry. The interaction of SPION–EGF conjugates with cells was analyzed in a C6 glioma cell culture. The distribution of the nanoparticles and their accumulation in tumors were assessed by magnetic resonance imaging in an orthotopic model of C6 gliomas. SPION–EGF nanosuspensions had the properties of a negative contrast agent with high coefficients of relaxation efficiency. In vitro studies of SPION–EGF nanoparticles showed high intracellular incorporation and the absence of a toxic influence on C6 cell viability and proliferation. Intravenous administration of SPION–EGF conjugates in animals provided receptor-mediated targeted delivery across the blood–brain barrier and tumor retention of the nanoparticles; this was more efficient than with unconjugated SPIONs. The accumulation of conjugates in the glioma was revealed as hypotensive zones on T2-weighted images with a twofold reduction in T2 relaxation time in comparison to unconjugated SPIONs (P<0.001). SPION–EGF conjugates provide targeted delivery and efficient magnetic resonance contrast enhancement of EGFR-overexpressing C6 gliomas.Keywords: brain tumor, C6 glioma, magnetic nanoparticles, EGFR, epidermal growth factor, MRI contrast agent, SPION
format article
author Shevtsov MA
Nikolaev BP
Yakovleva LY
Marchenko YY
Dobrodumov AV
Mikhrina AL
Martynova MG
Bystrova OA
Yakovenko IV
Ischenko AM
author_facet Shevtsov MA
Nikolaev BP
Yakovleva LY
Marchenko YY
Dobrodumov AV
Mikhrina AL
Martynova MG
Bystrova OA
Yakovenko IV
Ischenko AM
author_sort Shevtsov MA
title Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors
title_short Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors
title_full Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors
title_fullStr Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors
title_full_unstemmed Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors
title_sort superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (spion–egf) for targeting brain tumors
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/396a15a4b8584d33842f4a411a186f78
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