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Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice

About 30% of breast cancers metastasize to the brain; those widely disseminated are fatal typically in 3–4 months, even with the best available treatments, including surgery, drugs, and radiotherapy. To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumo...

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Autores principales: Hainfeld, James F., Ridwan, Sharif M., Stanishevskiy, F. Yaroslav, Smilowitz, Henry M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515899/
https://www.ncbi.nlm.nih.gov/pubmed/32973267
http://dx.doi.org/10.1038/s41598-020-72268-0
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author Hainfeld, James F.
Ridwan, Sharif M.
Stanishevskiy, F. Yaroslav
Smilowitz, Henry M.
author_facet Hainfeld, James F.
Ridwan, Sharif M.
Stanishevskiy, F. Yaroslav
Smilowitz, Henry M.
author_sort Hainfeld, James F.
collection PubMed
description About 30% of breast cancers metastasize to the brain; those widely disseminated are fatal typically in 3–4 months, even with the best available treatments, including surgery, drugs, and radiotherapy. To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumors after intravenous (IV) injection. The iodine then absorbs X-rays during radiotherapy (RT), creating free radicals and local tumor damage, effectively boosting the local RT dose at the tumor. Efficacy was tested using the very aggressive human triple negative breast cancer (TNBC, MDA-MB-231 cells) growing in the brains of athymic nude mice. With a well-tolerated non-toxic IV dose of the INPs (7 g iodine/kg body weight), tumors showed a heavily iodinated rim surrounding the tumor having an average uptake of 2.9% iodine by weight, with uptake peaks at 4.5%. This is calculated to provide a dose enhancement factor of approximately 5.5 (peaks at 8.0), the highest ever reported for any radiation-enhancing agents. With RT alone (15 Gy, single dose), all animals died by 72 days; INP pretreatment resulted in longer-term remissions with 40% of mice surviving 150 days and 30% surviving > 280 days.
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spelling pubmed-75158992020-09-29 Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice Hainfeld, James F. Ridwan, Sharif M. Stanishevskiy, F. Yaroslav Smilowitz, Henry M. Sci Rep Article About 30% of breast cancers metastasize to the brain; those widely disseminated are fatal typically in 3–4 months, even with the best available treatments, including surgery, drugs, and radiotherapy. To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumors after intravenous (IV) injection. The iodine then absorbs X-rays during radiotherapy (RT), creating free radicals and local tumor damage, effectively boosting the local RT dose at the tumor. Efficacy was tested using the very aggressive human triple negative breast cancer (TNBC, MDA-MB-231 cells) growing in the brains of athymic nude mice. With a well-tolerated non-toxic IV dose of the INPs (7 g iodine/kg body weight), tumors showed a heavily iodinated rim surrounding the tumor having an average uptake of 2.9% iodine by weight, with uptake peaks at 4.5%. This is calculated to provide a dose enhancement factor of approximately 5.5 (peaks at 8.0), the highest ever reported for any radiation-enhancing agents. With RT alone (15 Gy, single dose), all animals died by 72 days; INP pretreatment resulted in longer-term remissions with 40% of mice surviving 150 days and 30% surviving > 280 days. Nature Publishing Group UK 2020-09-24 /pmc/articles/PMC7515899/ /pubmed/32973267 http://dx.doi.org/10.1038/s41598-020-72268-0 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
Hainfeld, James F.
Ridwan, Sharif M.
Stanishevskiy, F. Yaroslav
Smilowitz, Henry M.
Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice
title Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice
title_full Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice
title_fullStr Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice
title_full_unstemmed Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice
title_short Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice
title_sort iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515899/
https://www.ncbi.nlm.nih.gov/pubmed/32973267
http://dx.doi.org/10.1038/s41598-020-72268-0
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