Gram Scale Production of Anisotropic Magnetic Nanoparticles for Magnetic Hyperthermia Treatment and Magnetic Particle Imaging

This dissertation presents my doctoral research conducted over the past three years at the Italian Institute of Technology (IIT) and the University of Genoa (UniGE). The work focuses on the development of magnetic nanoparticles (MNPs) in gram-scale production to enhance their magnetic properties for their use as heaters in magnetic hyperthermia treatment (MHT) and tracers in magnetic particle imaging (MPI) for cancer therapy. The use of the MNPs has been important in overcoming some of the limitations associated with traditional cancer treatments and diagnostics. One of key advantages of MHT is its ability to precisely target tumors, minimizing damage of healthy cells. However, despite its potential, MHT remains limited in clinical applications due to several challenges. The development of suitable MNPs is a critical factor, as the performance of MNPs is directly influenced by their structural properties. This work focuses on an in-depth investigation of the tuning of MNPs in terms of shape, size, and composition to enhance their magnetic performance and suitability for real applications. The chosen synthetic method, solvothermal synthesis, was previously explored in our earlier research, where the introduction of specific molecules acting as shape-directing agents allowed the control on the formation of cubic, hexagonal and star-like iron oxide NPs in a gram-scale mass production. In the present study, various shape-directing agent molecules were tested, along with the incorporation of metal dopants (Zn, Mn, Co, Ni) to further examine their impact on the magnetic properties of the MNPs. In order to increase the shape anisotropy of the NPs and, consequently, their magnetic performance, a combination of two shape-directing molecules was investigated. This approach led to the formation of a distinctive structure with high anisotropy constant, significantly improving heating efficiency and the overall performance for potential applications in both MHT and MPI. The resulting shape, referred to as ‘’Rubik’s cube NPs (NRKs), exhibits a predominantly cubic structure with an heterogeneous surface, further contributing to its enhanced magnetic properties. Furthermore, the synthesis process was optimized to fine-tune the dimensions of NRKs, ranging from 19 to 42 nm. To ensure stability in water and mimic a physiological environment, all investigated MNPs were functionalized with a biocompatible polymer. Among them, the NRKs demonstrated the highest heating efficiency and MPI performance, along with stability in viscous media designed to replicate the tumor microenvironment. Given these advantages, the NRKs were further explored as potential tracers for hyperthermia-guided MPI (h-MPI), a synergistic approach that enables precise tumor localization via MPI, followed by targeted treatment using magnetic MHT, with promising results, highlighting the potential for real-world applications.