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Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies

Glioblastoma (GBM) is a malignant brain tumour with a dismal prognosis, despite best treatment by surgical resection, radiation therapy (RT) and chemotherapy with temozolomide (TMZ). Nanoparticle (NP) therapy is an emerging consideration due to the ability of NPs to be formulated and cross the blood...

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Autores principales: Lu, Victor M., Jue, Toni Rose, McDonald, Kerrie L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584621/
https://www.ncbi.nlm.nih.gov/pubmed/33097778
http://dx.doi.org/10.1038/s41598-020-75372-3
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author Lu, Victor M.
Jue, Toni Rose
McDonald, Kerrie L.
author_facet Lu, Victor M.
Jue, Toni Rose
McDonald, Kerrie L.
author_sort Lu, Victor M.
collection PubMed
description Glioblastoma (GBM) is a malignant brain tumour with a dismal prognosis, despite best treatment by surgical resection, radiation therapy (RT) and chemotherapy with temozolomide (TMZ). Nanoparticle (NP) therapy is an emerging consideration due to the ability of NPs to be formulated and cross the blood brain barrier. Lanthanum oxide (La(2)O(3)) NPs are therapeutically advantageous due to the unique chemical properties of lanthanum making it cytotoxic to cancers, and able to enhance existing anti-cancer treatments. However, La(2)O(3) NPs have yet to be thoroughly investigated in brain tumors. We show that these NPs can reach the brain after venous injection, penetrate into GBM cells via endocytosis, dissociate to be cytotoxic, and enhance the therapeutic effects of RT and TMZ. The mechanisms of cell death by La(2)O(3) NPs were found to be multifaceted. Increasing NP concentration was correlated to increased intrinsic and extrinsic apoptosis pathway markers in a radical oxygen species (ROS)-dependent manner, as well as involving direct DNA damage and autophagic pathways within GBM patient-derived cell lines. NP interactions to sensitize GBM to RT and TMZ were shown to involve these pathways by enhancing ROS and apoptotic mechanisms. We therefore demonstrate the therapeutic potential of La(2)O(3) NPs to treat GBM cells in vitro, and encourage translational exploration in the future.
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spelling pubmed-75846212020-10-27 Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies Lu, Victor M. Jue, Toni Rose McDonald, Kerrie L. Sci Rep Article Glioblastoma (GBM) is a malignant brain tumour with a dismal prognosis, despite best treatment by surgical resection, radiation therapy (RT) and chemotherapy with temozolomide (TMZ). Nanoparticle (NP) therapy is an emerging consideration due to the ability of NPs to be formulated and cross the blood brain barrier. Lanthanum oxide (La(2)O(3)) NPs are therapeutically advantageous due to the unique chemical properties of lanthanum making it cytotoxic to cancers, and able to enhance existing anti-cancer treatments. However, La(2)O(3) NPs have yet to be thoroughly investigated in brain tumors. We show that these NPs can reach the brain after venous injection, penetrate into GBM cells via endocytosis, dissociate to be cytotoxic, and enhance the therapeutic effects of RT and TMZ. The mechanisms of cell death by La(2)O(3) NPs were found to be multifaceted. Increasing NP concentration was correlated to increased intrinsic and extrinsic apoptosis pathway markers in a radical oxygen species (ROS)-dependent manner, as well as involving direct DNA damage and autophagic pathways within GBM patient-derived cell lines. NP interactions to sensitize GBM to RT and TMZ were shown to involve these pathways by enhancing ROS and apoptotic mechanisms. We therefore demonstrate the therapeutic potential of La(2)O(3) NPs to treat GBM cells in vitro, and encourage translational exploration in the future. Nature Publishing Group UK 2020-10-23 /pmc/articles/PMC7584621/ /pubmed/33097778 http://dx.doi.org/10.1038/s41598-020-75372-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lu, Victor M.
Jue, Toni Rose
McDonald, Kerrie L.
Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies
title Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies
title_full Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies
title_fullStr Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies
title_full_unstemmed Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies
title_short Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies
title_sort cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584621/
https://www.ncbi.nlm.nih.gov/pubmed/33097778
http://dx.doi.org/10.1038/s41598-020-75372-3
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