Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors

Marcus Stapf, Ulf Teichgräber, Ingrid Hilger Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany Abstract: Heat-based approaches have been considered as promising tools due...

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Autores principales:	Stapf M, Teichgräber U, Hilger I
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	bladder cancer magnetic heating magnetic nanoparticles methotrexate hyperthermia mouse xenograft Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9a42285b20d34e84aa867c57ac630bbe
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spelling	oai:doaj.org-article:9a42285b20d34e84aa867c57ac630bbe2021-12-02T00:07:20ZMethotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors1178-2013https://doaj.org/article/9a42285b20d34e84aa867c57ac630bbe2017-04-01T00:00:00Zhttps://www.dovepress.com/methotrexate-coupled-nanoparticles-and-magnetic-nanochemothermia-for-t-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Marcus Stapf, Ulf Teichgräber, Ingrid Hilger Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany Abstract: Heat-based approaches have been considered as promising tools due to their ability to directly eradicate tumor cells and/or increase the sensitivity of tumors to radiation- or chemotherapy. In particular, the heating of magnetic nanoparticles (MNPs) via an alternating magnetic field can provide a handy alternative for a localized tumor treatment. To amplify the efficacy of magnetically induced thermal treatments, we elucidated the superior tumor-destructive effect of methotrexate-coupled MNPs (MTX/MNPs) in combination with magnetic heating (nanochemothermia) over the thermal treatment alone. Our studies in a murine bladder xenograft model revealed the enormous potential of nanochemothermia for a localized and relapse-free destruction of tumors which was superior to the thermal treatment alone. Nanochemothermia remarkably fostered the reduction of tumor volume. It impaired proapoptotic signaling (eg, p-p53), cell survival (eg, p-ERK1/2), and cell cycle (cyclins) pathways. Additionally, heat shock proteins (eg, HSP70) were remarkably affected. Moreover, nanochemothermia impaired the induction of angiogenic signaling by decreasing, for example, the levels of VEGF-R1 and MMP9, although an increasing tumor hypoxia was indicated by elevated Hif-1α levels. In contrast, tumor cells were able to recover after the thermal treatments alone. In conclusion, nanochemothermia on the basis of MTX/MNPs was superior to the thermal treatment due to a modification of cellular pathways, particularly those associated with the cellular survival and tumor vasculature. This allowed very efficient and relapse-free destruction of tumors. Keywords: bladder cancer, magnetic heating, magnetic nanoparticles, methotrexate, hyperthermia, mouse xenograftStapf MTeichgräber UHilger IDove Medical Pressarticlebladder cancermagnetic heatingmagnetic nanoparticlesmethotrexatehyperthermiamouse xenograftMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2793-2811 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	bladder cancer magnetic heating magnetic nanoparticles methotrexate hyperthermia mouse xenograft Medicine (General) R5-920
spellingShingle	bladder cancer magnetic heating magnetic nanoparticles methotrexate hyperthermia mouse xenograft Medicine (General) R5-920 Stapf M Teichgräber U Hilger I Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors
description	Marcus Stapf, Ulf Teichgräber, Ingrid Hilger Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany Abstract: Heat-based approaches have been considered as promising tools due to their ability to directly eradicate tumor cells and/or increase the sensitivity of tumors to radiation- or chemotherapy. In particular, the heating of magnetic nanoparticles (MNPs) via an alternating magnetic field can provide a handy alternative for a localized tumor treatment. To amplify the efficacy of magnetically induced thermal treatments, we elucidated the superior tumor-destructive effect of methotrexate-coupled MNPs (MTX/MNPs) in combination with magnetic heating (nanochemothermia) over the thermal treatment alone. Our studies in a murine bladder xenograft model revealed the enormous potential of nanochemothermia for a localized and relapse-free destruction of tumors which was superior to the thermal treatment alone. Nanochemothermia remarkably fostered the reduction of tumor volume. It impaired proapoptotic signaling (eg, p-p53), cell survival (eg, p-ERK1/2), and cell cycle (cyclins) pathways. Additionally, heat shock proteins (eg, HSP70) were remarkably affected. Moreover, nanochemothermia impaired the induction of angiogenic signaling by decreasing, for example, the levels of VEGF-R1 and MMP9, although an increasing tumor hypoxia was indicated by elevated Hif-1α levels. In contrast, tumor cells were able to recover after the thermal treatments alone. In conclusion, nanochemothermia on the basis of MTX/MNPs was superior to the thermal treatment due to a modification of cellular pathways, particularly those associated with the cellular survival and tumor vasculature. This allowed very efficient and relapse-free destruction of tumors. Keywords: bladder cancer, magnetic heating, magnetic nanoparticles, methotrexate, hyperthermia, mouse xenograft
format	article
author	Stapf M Teichgräber U Hilger I
author_facet	Stapf M Teichgräber U Hilger I
author_sort	Stapf M
title	Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors
title_short	Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors
title_full	Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors
title_fullStr	Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors
title_full_unstemmed	Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors
title_sort	methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of t24 bladder tumors
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/9a42285b20d34e84aa867c57ac630bbe
work_keys_str_mv	AT stapfm methotrexatecouplednanoparticlesandmagneticnanochemothermiafortherelapsefreetreatmentoft24bladdertumors AT teichgraberu methotrexatecouplednanoparticlesandmagneticnanochemothermiafortherelapsefreetreatmentoft24bladdertumors AT hilgeri methotrexatecouplednanoparticlesandmagneticnanochemothermiafortherelapsefreetreatmentoft24bladdertumors
_version_	1718403943598391296

Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors

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