Fe3O4 Nanoparticles and Paraffin Wax as Phase Change Materials Embedded in Polymer Matrixes for Temperature-Controlled Magnetic Hyperthermia

Over the last 2 decades, magnetic hyperthermia (MH) has been recognized as a promising concept for efficient cancer treatment. Recently, it has been receiving increased attention because of its procedure simplicity, noninvasive nature, and effective solid tumor heating with minimal damage to healthy surrounding normal tissues. In this paper, we report about the development of theranostic superparamagnetic iron oxide nanoclusters, demonstrating efficient heating in hyperthermia and good response under a magnetic resonance imaging (MRI) scan. Multiple cores of 25 +/- 2 nm superparamagnetic iron oxide (Fe3O4) nanoparticles and paraffin wax based on 24-hydrocarbon chains (tetracosane), used as a phase change material, were coencapsulated in an interior core of a self-assembled PEO-PPO-PEO polymer and subsequently covalently coated by 20 kDa branched poly(ethylene glycol), resulting in 135 +/- 10 nm hydrodynamic diameter nanoclusters. The synthesized nanoclusters were found to have good stability in phosphate-buffered saline. The physicochemical and magnetic properties of the nanoclusters exhibit an efficient magnetic-to-thermal energy conversion with self-regulation of the hyperthermia temperature. Under irradiation to an alternating magnetic field (AMF) of 33 kA/m at a frequency of 300 kHz, the nanoclusters demonstrate a specific absorption rate (SAR) of 475 +/- 17 W/g. The nanoclusters also exhibit a high transverse relaxivity of 68 (mM s)(-1) at 1.5 T MRI. In preclinical studies, nanoclusters were intravenously injected to mice bearing 4T1 triple negative breast carcinoma lung metastases. Mice were irradiated by an AMF to demonstrate the antitumor efficacy, with 66% reduction in the number of metastases, which pave the route for the application of effective hyperthermia treatment for a metastatic cancer model.