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Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model

Sarah Nanoparticles (SaNPs) are unique multicore iron oxide-based nanoparticles, developed for the treatment of advanced cancer, following standard care, through the selective delivery of thermal energy to malignant cells upon exposure to an alternating magnetic field. For their therapeutic effect,...

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Autores principales: Kraus, Sarah, Khandadash, Raz, Hof, Raphael, Nyska, Abraham, Sigalov, Ekaterina, Eltanani, Moshe, Rukenstein, Pazit, Rabinovitz, Ricarina, Kassem, Rana, Antebi, Adam, Shalev, Ofer, Cohen-Erner, Moshe, Goss, Glenwood, Cyjon, Arnoldo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602876/
https://www.ncbi.nlm.nih.gov/pubmed/34804962
http://dx.doi.org/10.3389/fonc.2021.761045
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author Kraus, Sarah
Khandadash, Raz
Hof, Raphael
Nyska, Abraham
Sigalov, Ekaterina
Eltanani, Moshe
Rukenstein, Pazit
Rabinovitz, Ricarina
Kassem, Rana
Antebi, Adam
Shalev, Ofer
Cohen-Erner, Moshe
Goss, Glenwood
Cyjon, Arnoldo
author_facet Kraus, Sarah
Khandadash, Raz
Hof, Raphael
Nyska, Abraham
Sigalov, Ekaterina
Eltanani, Moshe
Rukenstein, Pazit
Rabinovitz, Ricarina
Kassem, Rana
Antebi, Adam
Shalev, Ofer
Cohen-Erner, Moshe
Goss, Glenwood
Cyjon, Arnoldo
author_sort Kraus, Sarah
collection PubMed
description Sarah Nanoparticles (SaNPs) are unique multicore iron oxide-based nanoparticles, developed for the treatment of advanced cancer, following standard care, through the selective delivery of thermal energy to malignant cells upon exposure to an alternating magnetic field. For their therapeutic effect, SaNPs need to accumulate in the tumor. Since the potential accumulation and associated toxicity in normal tissues are an important risk consideration, biodistribution and toxicity were assessed in naïve BALB/c mice. Therapeutic efficacy and the effect on survival were investigated in the 4T1 murine model of metastatic breast cancer. Toxicity evaluation at various timepoints did not reveal any abnormal clinical signs, evidence of alterations in organ function, nor histopathologic adverse target organ toxicity, even after a follow up period of 25 weeks, confirming the safety of SaNP use. The biodistribution evaluation, following SaNP administration, indicated that SaNPs accumulate mainly in the liver and spleen. A comprehensive pharmacokinetics evaluation, demonstrated that the total percentage of SaNPs that accumulated in the blood and vital organs was ~78%, 46%, and 36% after 4, 13, and 25 weeks, respectively, suggesting a time-dependent clearance from the body. Efficacy studies in mice bearing 4T1 metastatic tumors revealed a 49.6% and 70% reduction in the number of lung metastases and their relative size, respectively, in treated vs. control mice, accompanied by a decrease in tumor cell viability in response to treatment. Moreover, SaNP treatment followed by alternating magnetic field exposure significantly improved the survival rate of treated mice compared to the controls. The median survival time was 29 ± 3.8 days in the treated group vs. 21.6 ± 4.9 days in the control, p-value 0.029. These assessments open new avenues for generating SaNPs and alternating magnetic field application as a potential novel therapeutic modality for metastatic cancer patients.
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spelling pubmed-86028762021-11-20 Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model Kraus, Sarah Khandadash, Raz Hof, Raphael Nyska, Abraham Sigalov, Ekaterina Eltanani, Moshe Rukenstein, Pazit Rabinovitz, Ricarina Kassem, Rana Antebi, Adam Shalev, Ofer Cohen-Erner, Moshe Goss, Glenwood Cyjon, Arnoldo Front Oncol Oncology Sarah Nanoparticles (SaNPs) are unique multicore iron oxide-based nanoparticles, developed for the treatment of advanced cancer, following standard care, through the selective delivery of thermal energy to malignant cells upon exposure to an alternating magnetic field. For their therapeutic effect, SaNPs need to accumulate in the tumor. Since the potential accumulation and associated toxicity in normal tissues are an important risk consideration, biodistribution and toxicity were assessed in naïve BALB/c mice. Therapeutic efficacy and the effect on survival were investigated in the 4T1 murine model of metastatic breast cancer. Toxicity evaluation at various timepoints did not reveal any abnormal clinical signs, evidence of alterations in organ function, nor histopathologic adverse target organ toxicity, even after a follow up period of 25 weeks, confirming the safety of SaNP use. The biodistribution evaluation, following SaNP administration, indicated that SaNPs accumulate mainly in the liver and spleen. A comprehensive pharmacokinetics evaluation, demonstrated that the total percentage of SaNPs that accumulated in the blood and vital organs was ~78%, 46%, and 36% after 4, 13, and 25 weeks, respectively, suggesting a time-dependent clearance from the body. Efficacy studies in mice bearing 4T1 metastatic tumors revealed a 49.6% and 70% reduction in the number of lung metastases and their relative size, respectively, in treated vs. control mice, accompanied by a decrease in tumor cell viability in response to treatment. Moreover, SaNP treatment followed by alternating magnetic field exposure significantly improved the survival rate of treated mice compared to the controls. The median survival time was 29 ± 3.8 days in the treated group vs. 21.6 ± 4.9 days in the control, p-value 0.029. These assessments open new avenues for generating SaNPs and alternating magnetic field application as a potential novel therapeutic modality for metastatic cancer patients. Frontiers Media S.A. 2021-11-05 /pmc/articles/PMC8602876/ /pubmed/34804962 http://dx.doi.org/10.3389/fonc.2021.761045 Text en Copyright © 2021 Kraus, Khandadash, Hof, Nyska, Sigalov, Eltanani, Rukenstein, Rabinovitz, Kassem, Antebi, Shalev, Cohen-Erner, Goss and Cyjon https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Kraus, Sarah
Khandadash, Raz
Hof, Raphael
Nyska, Abraham
Sigalov, Ekaterina
Eltanani, Moshe
Rukenstein, Pazit
Rabinovitz, Ricarina
Kassem, Rana
Antebi, Adam
Shalev, Ofer
Cohen-Erner, Moshe
Goss, Glenwood
Cyjon, Arnoldo
Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model
title Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model
title_full Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model
title_fullStr Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model
title_full_unstemmed Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model
title_short Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model
title_sort novel nanoparticle-based cancer treatment, effectively inhibits lung metastases and improves survival in a murine breast cancer model
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602876/
https://www.ncbi.nlm.nih.gov/pubmed/34804962
http://dx.doi.org/10.3389/fonc.2021.761045
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