Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Marcus Stapf,* Nadine Pömpner,* Ulf Teichgräber, Ingrid HilgerInstitute of Diagnostic and Interventional Radiology, Department of Experimental Radiology, Jena University Hospital, Friedrich-Schiller University, Jena, Germany*These authors contributed equally to this workAb...

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Autores principales:	Stapf M, Pömpner N, Teichgräber U, Hilger I
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	magnetic nanoparticles (MNP) SPION in vitro methotrexate (MTX) hyperthermia breast cancer bladder cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d679c4e0eb4b4cf98cf903772c728c71
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spelling	oai:doaj.org-article:d679c4e0eb4b4cf98cf903772c728c712021-12-02T03:58:36ZHeterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia1178-2013https://doaj.org/article/d679c4e0eb4b4cf98cf903772c728c712016-02-01T00:00:00Zhttps://www.dovepress.com/heterogeneous-response-of-different-tumor-cell-lines-to-methotrexate-c-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Marcus Stapf,* Nadine Pömpner,* Ulf Teichgräber, Ingrid HilgerInstitute of Diagnostic and Interventional Radiology, Department of Experimental Radiology, Jena University Hospital, Friedrich-Schiller University, Jena, Germany*These authors contributed equally to this workAbstract: Today, the therapeutic efficacy of cancer is restricted by the heterogeneity of the response of tumor cells to chemotherapeutic drugs. Since those therapies are also associated with severe side effects in nontarget organs, the application of drugs in combination with nanocarriers for targeted therapy has been suggested. Here, we sought to assess whether the coupling of methotrexate (MTX) to magnetic nanoparticles (MNP) could serve as a valuable tool to circumvent the heterogeneity of tumor cell response to MTX by the combined treatment with hyperthermia. To this end, we investigated five breast cancer cell lines of different origin and with different mutational statuses, as well as a bladder cancer cell line in terms of their response to exposure to MTX as a free drug or after its coupling to MNP as well as in presence/absence of hyperthermia. We also assessed whether the effects could be connected to the cell line-specific expression of proteins related to the uptake and efflux of MTX and MNP. Our results revealed a very heterogeneous and cell line-dependent response to an exposure with MTX-coupled MNP (MTX–MNP), which was almost comparable to the efficacy of free MTX in the same cell line. Moreover, a cell line-specific and preferential uptake of MTX–MNP compared with MNP alone was found (probably by receptor-mediated endocytosis), agreeing with the observed cytotoxic effects. Opposed to this, the expression pattern of several cell membrane transport proteins noted for MTX uptake and efflux was only by tendency in agreement with the cellular toxicity of MTX–MNP in different cell lines. Higher cytotoxic effects were achieved by exposing cells to a combination of MTX–MNP and hyperthermal treatment, compared with MTX or thermotherapy alone. However, the heterogeneity in the response of the tumor cell lines to MTX could not be completely abolished – even after its combination with MNP and/or hyperthermia – and the application of higher thermal dosages might be necessary.Keywords: magnetic nanoparticles, SPION, in vitro, methotrexate, hyperthermia, breast cancer, bladder cancerStapf MPömpner NTeichgräber UHilger IDove Medical Pressarticlemagnetic nanoparticles (MNP)SPIONin vitromethotrexate (MTX)hyperthermiabreast cancerbladder cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss Issue 1, Pp 485-500 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	magnetic nanoparticles (MNP) SPION in vitro methotrexate (MTX) hyperthermia breast cancer bladder cancer Medicine (General) R5-920
spellingShingle	magnetic nanoparticles (MNP) SPION in vitro methotrexate (MTX) hyperthermia breast cancer bladder cancer Medicine (General) R5-920 Stapf M Pömpner N Teichgräber U Hilger I Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia
description	Marcus Stapf,* Nadine Pömpner,* Ulf Teichgräber, Ingrid HilgerInstitute of Diagnostic and Interventional Radiology, Department of Experimental Radiology, Jena University Hospital, Friedrich-Schiller University, Jena, Germany*These authors contributed equally to this workAbstract: Today, the therapeutic efficacy of cancer is restricted by the heterogeneity of the response of tumor cells to chemotherapeutic drugs. Since those therapies are also associated with severe side effects in nontarget organs, the application of drugs in combination with nanocarriers for targeted therapy has been suggested. Here, we sought to assess whether the coupling of methotrexate (MTX) to magnetic nanoparticles (MNP) could serve as a valuable tool to circumvent the heterogeneity of tumor cell response to MTX by the combined treatment with hyperthermia. To this end, we investigated five breast cancer cell lines of different origin and with different mutational statuses, as well as a bladder cancer cell line in terms of their response to exposure to MTX as a free drug or after its coupling to MNP as well as in presence/absence of hyperthermia. We also assessed whether the effects could be connected to the cell line-specific expression of proteins related to the uptake and efflux of MTX and MNP. Our results revealed a very heterogeneous and cell line-dependent response to an exposure with MTX-coupled MNP (MTX–MNP), which was almost comparable to the efficacy of free MTX in the same cell line. Moreover, a cell line-specific and preferential uptake of MTX–MNP compared with MNP alone was found (probably by receptor-mediated endocytosis), agreeing with the observed cytotoxic effects. Opposed to this, the expression pattern of several cell membrane transport proteins noted for MTX uptake and efflux was only by tendency in agreement with the cellular toxicity of MTX–MNP in different cell lines. Higher cytotoxic effects were achieved by exposing cells to a combination of MTX–MNP and hyperthermal treatment, compared with MTX or thermotherapy alone. However, the heterogeneity in the response of the tumor cell lines to MTX could not be completely abolished – even after its combination with MNP and/or hyperthermia – and the application of higher thermal dosages might be necessary.Keywords: magnetic nanoparticles, SPION, in vitro, methotrexate, hyperthermia, breast cancer, bladder cancer
format	article
author	Stapf M Pömpner N Teichgräber U Hilger I
author_facet	Stapf M Pömpner N Teichgräber U Hilger I
author_sort	Stapf M
title	Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia
title_short	Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia
title_full	Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia
title_fullStr	Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia
title_full_unstemmed	Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia
title_sort	heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/d679c4e0eb4b4cf98cf903772c728c71
work_keys_str_mv	AT stapfm heterogeneousresponseofdifferenttumorcelllinestomethotrexatecouplednanoparticlesinpresenceofhyperthermia AT pompnern heterogeneousresponseofdifferenttumorcelllinestomethotrexatecouplednanoparticlesinpresenceofhyperthermia AT teichgraberu heterogeneousresponseofdifferenttumorcelllinestomethotrexatecouplednanoparticlesinpresenceofhyperthermia AT hilgeri heterogeneousresponseofdifferenttumorcelllinestomethotrexatecouplednanoparticlesinpresenceofhyperthermia
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Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

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