Assembly of Iron Oxide Nanocubes for Enhanced Cancer Hyperthermia and Magnetic Resonance Imaging

Multiple formulations of iron oxide nanoparticles (IONPs) have been proposed for enhancing contrast in magnetic resonance imaging (MRI) and for increasing efficacy in thermal ablation therapies. However, insufficient accumulation at the disease site and low magnetic performance hamper the clinical application of IONPs. Here, 20 nm iron oxide nanocubes were assembled into larger nanoconstructs externally stabilized by a serum albumin coating. The resulting assemblies of nanocubes (ANCs) had an average diameter of 100 nm and exhibited transverse relaxivity (r(2) = 678.9 ± 29.0 mM(‒1)·s(‒1) at 1.41 T) and heating efficiency (specific absorption rate of 109.8 ± 12.8 W·g(‒1) at 512 kHz and 10 kA·m(‒1)). In mice bearing glioblastoma multiforme tumors, Cy5.5-labeled ANCs allowed visualization of malignant masses via both near infrared fluorescent and magnetic resonance imaging. Also, upon systemic administration of ANCs (5 mg(Fe)·kg(‒1)), 30 min of daily exposure to alternating magnetic fields for three consecutive days was sufficient to halt tumor progression. This study demonstrates that intravascular administration of ANCs can effectively visualize and treat neoplastic masses.