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

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 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.

A Validated Methodological Approach to Prove the Safety of Clinical Electromagnetic Induction Systems in Magnetic Hyperthermia

“…The MNH system presented in this study introduces a method of regional irradiation, treating the patient's entire torso, thus eliminating the need for precise tumor detection and localization. This approach, combined with the intravenous injection of MNPs, which accumulate around tumors due to the EPR effect [20], facilitates the treatment of multiple tumors, including undetected micro-tumors, across various torso locations, thus not being organ specific.…”

“…The Sarah Nanotechnology System is a medical device developed by New Phase Ltd. to treat stage IV metastatic solid tumors through the delivery of thermal energy to malignant cells, thereby causing hyperthermic cancer cell death at sub-ablative temperatures [19,20]. The system involves two main components, MNPs named Sarah nanoparticles (SaNPs) and an Electromagnetic Induction System (EIS).…”

Delivery and assessment of a CRISPR/nCas9-based genome editing system on in vitro models of mucopolysaccharidoses IVA assisted by magnetite-based nanoparticles

“…The surface composition of non-viral vectors is crucial for biodistribution 45 . For example, iron-based nanoparticles exhibiting zeta potential ranging − 30 to + 11.57 mV and sizes ranging from 135 to 221 nm have shown an increased internalization on in vitro assays, and with preference liver storage has been found in the liver for in vivo approaches 46 , 47 . Since our MLPs showed a hydrodynamic diameter of 247 nm and Z-potential of − 38.9 ± 2.4 mV (Fig.…”

Toxoplasma gondii-derived antigen modifies tumor microenvironment of Ehrlich solid carcinoma murine model and enhances immunotherapeutic activity of cyclophosphamide

“…All tumor samples were fixed in 10% buffered formalin, processed for histopathological examination by H&E staining, and Masson trichrome to assess the degree of fibrosis. Evaluation of the stained sections to assess degree of fibrosis and necrosis was performed using a semiquantitative grading system, as described previously with some modifications [ 27 , 28 ]. Histopathological examination was performed in a blind manner.…”