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.
Highlights
Cancer is a major public health problem worldwide and is the leading cause of death in the Western world with a resultant significant detrimental economic impact [1]
transmission electron microscope (TEM) imaging demonstrated that Sarah Nanoparticles (SaNPs), containing several encapsulated 25 nm iron oxide (IO) nanoparticles, exhibit a monodisperse state and amorphous or spherical shapes
The results demonstrated that SaNPs were primarily accumulated in the mononuclear phagocyte system (MPS), with the liver having the highest SaNP accumulation per organ weight
Summary
Cancer is a major public health problem worldwide and is the leading cause of death in the Western world with a resultant significant detrimental economic impact [1]. In the metastatic setting are limited and better treatments are needed. Recent improvement in nanomaterials and the rapid development of nanotechnology provide an opportunity for new therapeutic strategies against cancer. Nanoparticles are promising due to their good biocompatibility, based on their particle size, shape, and physicochemical properties [2]. A rapidly growing body of literature has provided evidence suggesting a major role for nanotechnology in cancer treatment. A variety of nanoparticles have been investigated as drug carriers, photothermal agents, contrast agents, and radiosensitizers [3]. Of particular interest are their unique chemical properties, including the ability to bind amine and thiol groups, allowing surface modification and use in biomedical applications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
