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 TITLE=Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.761045 DOI=10.3389/fonc.2021.761045 ISSN=2234-943X ABSTRACT=
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