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Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells

Nanotechnology-based approaches hold substantial potential to avoid chemoresistance and minimize side effects. In this work, we have used biocompatible iron oxide magnetic nanoparticles (MNPs) called MF66 and functionalized with the antineoplastic drug doxorubicin (DOX) against MDA-MB-231 cells. Ele...

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Autores principales: Lazaro-Carrillo, Ana, Calero, Macarena, Aires, Antonio, L. Cortajarena, Aitziber, Simões, Bruno M., Latorre, Alfonso, Somoza, Álvaro, Clarke, Robert B., Miranda, Rodolfo, Villanueva, Angeles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352336/
https://www.ncbi.nlm.nih.gov/pubmed/32485849
http://dx.doi.org/10.3390/cancers12061397
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author Lazaro-Carrillo, Ana
Calero, Macarena
Aires, Antonio
L. Cortajarena, Aitziber
Simões, Bruno M.
Latorre, Alfonso
Somoza, Álvaro
Clarke, Robert B.
Miranda, Rodolfo
Villanueva, Angeles
author_facet Lazaro-Carrillo, Ana
Calero, Macarena
Aires, Antonio
L. Cortajarena, Aitziber
Simões, Bruno M.
Latorre, Alfonso
Somoza, Álvaro
Clarke, Robert B.
Miranda, Rodolfo
Villanueva, Angeles
author_sort Lazaro-Carrillo, Ana
collection PubMed
description Nanotechnology-based approaches hold substantial potential to avoid chemoresistance and minimize side effects. In this work, we have used biocompatible iron oxide magnetic nanoparticles (MNPs) called MF66 and functionalized with the antineoplastic drug doxorubicin (DOX) against MDA-MB-231 cells. Electrostatically functionalized MNPs showed effective uptake and DOX linked to MNPs was more efficiently retained inside the cells than free DOX, leading to cell inactivation by mitotic catastrophe, senescence and apoptosis. Both effects, uptake and cytotoxicity, were demonstrated by different assays and videomicroscopy techniques. Likewise, covalently functionalized MNPs using three different linkers—disulfide (DOX-S-S-Pyr, called MF66-S-S-DOX), imine (DOX-I-Mal, called MF66-I-DOX) or both (DOX-I-S-S-Pyr, called MF66-S-S-I-DOX)—were also analysed. The highest cell death was detected using a linker sensitive to both pH and reducing environment (DOX-I-S-S-Pyr). The greatest success of this study was to detect also their activity against breast cancer stem-like cells (CSC) from MDA-MB-231 and primary breast cancer cells derived from a patient with a similar genetic profile (triple-negative breast cancer). In summary, these nanoformulations are promising tools as therapeutic agent vehicles, due to their ability to produce efficient internalization, drug delivery, and cancer cell inactivation, even in cancer stem-like cells (CSCs) from patients.
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spelling pubmed-73523362020-07-15 Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells Lazaro-Carrillo, Ana Calero, Macarena Aires, Antonio L. Cortajarena, Aitziber Simões, Bruno M. Latorre, Alfonso Somoza, Álvaro Clarke, Robert B. Miranda, Rodolfo Villanueva, Angeles Cancers (Basel) Article Nanotechnology-based approaches hold substantial potential to avoid chemoresistance and minimize side effects. In this work, we have used biocompatible iron oxide magnetic nanoparticles (MNPs) called MF66 and functionalized with the antineoplastic drug doxorubicin (DOX) against MDA-MB-231 cells. Electrostatically functionalized MNPs showed effective uptake and DOX linked to MNPs was more efficiently retained inside the cells than free DOX, leading to cell inactivation by mitotic catastrophe, senescence and apoptosis. Both effects, uptake and cytotoxicity, were demonstrated by different assays and videomicroscopy techniques. Likewise, covalently functionalized MNPs using three different linkers—disulfide (DOX-S-S-Pyr, called MF66-S-S-DOX), imine (DOX-I-Mal, called MF66-I-DOX) or both (DOX-I-S-S-Pyr, called MF66-S-S-I-DOX)—were also analysed. The highest cell death was detected using a linker sensitive to both pH and reducing environment (DOX-I-S-S-Pyr). The greatest success of this study was to detect also their activity against breast cancer stem-like cells (CSC) from MDA-MB-231 and primary breast cancer cells derived from a patient with a similar genetic profile (triple-negative breast cancer). In summary, these nanoformulations are promising tools as therapeutic agent vehicles, due to their ability to produce efficient internalization, drug delivery, and cancer cell inactivation, even in cancer stem-like cells (CSCs) from patients. MDPI 2020-05-29 /pmc/articles/PMC7352336/ /pubmed/32485849 http://dx.doi.org/10.3390/cancers12061397 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lazaro-Carrillo, Ana
Calero, Macarena
Aires, Antonio
L. Cortajarena, Aitziber
Simões, Bruno M.
Latorre, Alfonso
Somoza, Álvaro
Clarke, Robert B.
Miranda, Rodolfo
Villanueva, Angeles
Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells
title Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells
title_full Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells
title_fullStr Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells
title_full_unstemmed Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells
title_short Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells
title_sort tailored functionalized magnetic nanoparticles to target breast cancer cells including cancer stem-like cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352336/
https://www.ncbi.nlm.nih.gov/pubmed/32485849
http://dx.doi.org/10.3390/cancers12061397
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