Synthesis and modeling of manganese ferrite nanoparticles for magnetic hyperthermia applications

Biologically targeted magnetic hyperthermia (MH) is a promising cancer therapeutic that is both non-invasive and has the potential to serve as a single-modality cancer treatment. MH operates through the elevation of temperatures between 40-43 °C to induce apoptosis in malignant tumor cells, while the small size of the magnetic nanoparticles preserves the healthy surrounding tissue. At present, MH is limited by low heating efficiency and heterogenous outcomes, and treatment requires direct-injection of the nanoparticles, excluding deep-tissue and metastatic tumors from the therapy. The most popular candidates for MH are the spinel ferrites iron oxide and manganese iron oxide (MFO). These materials have been extensively discussed in the literature, but at present, no significant relationship has been identified between synthetic method, material properties, and in vivo efficacy. Synthesis at the nanoscale imparts a variety of novel properties on a material, and difficulty in characterizing many of these features has led to a poor understanding of how to tailor MFO for clinical applications. In order for MH to be realized as a standalone clinical theranostic, several variables must be targeted. In particular, the saturation magnetization (MS) of the material must be maximized for in vivo applications. MS can be influenced by a variety of parameters that are highly dependent on synthetic condition. Synthetic modifications were made to a facile polyol route in order to build a material model of MFO using principal component analysis (PCA). Nanoparticles with average crystallite sizes ranging from 4.8 to 12.3 nm were synthesized through a variety of conditions and served as inputs for the PCA. This exploratory analysis aided in identifying which synthetic variations most influenced material properties. A subset of samples was selected based on the PCA results for further magnetic characterization, which enabled the identification of a single synthetic methodology that maximized MS for the series. This work addresses several inconsistencies in existing literature regarding MH candidates, and reports on the synthetic parameters necessary to maximize the MS of MFO nanoparticles. It was found that synthetic conditions played the most significant role in altering material properties, while previously identified factors such as crystallite size were less influential. The optimized synthetic strategy presented herein serves as a blueprint for future work in enabling MH as a standalone treatment for cancer