Designing Nanoparticles for Image-Guided and Depth-Independent Magnetothermal Therapy of the Brain Tumors

Using molecular gadolinium-based contrast agents for magnetic resonance imaging (MRI) raises major concerns for glioblastoma multiforme (GBM) patients suffering from chronic kidney disease due to their high renal clearance and toxicity. Iron oxide nanoparticle contrast agents do not show any renal clearance due to their larger size and therefore are suitable contrast agents for imaging of brain tumors in these patients. Also, they can generate controlled amount of heat in response to magnetic fields, which can be used for simultaneous imaging and therapy of these tumors. However, tuning the physicochemical characteristics of these nanoparticles is essential to achieve the required imaging contrast and magnetic heating. Here, we will first demonstrate how a new imaging technique, called magnetic particle imaging (MPI) can be used for safer GBM imaging using these optimized nanoparticles. Then, we will show how the nanoparticles size, phase purity and crystallographic structure can define their magnetothermal efficiency. We have investigated our approach for imaging of several types of brain tumors with different levels of aggressiveness, to identify the effective functionality of these nanoparticles in different brain tumor microenvironments. Our nanoparticles enabled high resolution (i.e., ~600 µm) imaging with ultra-high contrast agent mass sensitivity of less than ~550pg Fe/µL. They enabled three-dimensional targeted imaging of the orthotopic brain tumors in mice after their intravenous injection. Iron oxide nanoparticles have been approved by FDA for a variety of biomedical applications and we envision that our optimized contrast agents will ultimately find clinical applications for safer and more effective brain tumor imaging.