Surface-engineered Superparamagnetic Iron Oxide Nanoparticles as Superior Biomedical Imaging Agents
Creators: name: Kaur, Satnam
Publisher: name: RMIT University
Year: 2025
Subjects: classificationCode: 310607
subject: Nanobiotechnology

description: Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as an integral component in the advancement of biomedical imaging technologies, particularly due to their desirable magnetic properties and compatibility with biological systems. These nanoparticles hold the promise of revolutionizing magnetic particle imaging (MPI) and magnetic resonance imaging (MRI) by providing enhanced contrast, which is paramount for the accurate diagnosis and treatment of various biomedical conditions. The ability to manipulate their magnetic behavior at the nanoscale presents unprecedented opportunities in the field of nanomedicine. Despite these attractive features, the full clinical potential of SPIONs remains unrealized, as a vast range of factors can influence their performance, leading to challenges in producing optimum SPIONs for biomedical applications. This thesis aims to bridge the existing gaps by proposing innovative approaches to controllably synthesize and tune the characteristics of SPIONs, enhancing their applicability as contrast agents.
The synthesis of SPIONs in high boiling point solvents can produce nanoparticles of uniform size and shape, but these processes often result in nanoparticles with hydrophobic surfaces. This hydrophobicity is a critical barrier to the successful integration of SPIONs into aqueous biological environments and poor control over the aqueous dispersibility of SPIONs can lead to rapid clearance from the body, aggregation, and suboptimal interaction with target tissues. Moreover, the surface of SPIONs is prone to oxidation, which can result in a magnetic dead layer that can severely compromise their magnetic properties. Recognizing these limitations, this thesis sets out to redefine the synthesis, solvent phase transfer, and surface modification processes to produce SPIONs that are not only hydrophilic but also maintain their magnetic integrity upon exposure to physiological conditions.
One of the key methodologies eventuated from this research is grounded in the innovative use of triethylamine as an amphiphilic surfactant for the phase transfer of oleic acid-capped SPIONs. This approach facilitates a highly effective transition of SPIONs from an organic to an aqueous medium, promoting their compatibility with biological systems. A combination of unique ligand exchange and rearrangement mechanisms during the phase transfer process leads to the spontaneous formation of liposomes around the SPIONs, effectively mimicking the structure and stability of natural Magnetosomes. The research reveals that the triethylamine-mediated phase transfer method successfully produces artificial Magnetosomes with dynamic stability and superior magnetic properties compared to their hydrophobic counterparts. These desirable features are then exploited by assessing the potential of these synthetic Magnetosomes as MPI tracers and T2 MRI contrast agents.
The next part of the research explores how doping of cobalt in the lattice of SPIONs, in combination with their liposomal encapsulation, impacts their magnetic and other physicochemical properties. The significantly boosted performance of this system is then explored for potential application as an MPI tracer.
Both above investigations provided strong indications that surface characteristics of SPIONs can play a non-trivial role in their magnetic behavior and magnetic field-assisted imaging application. However, considering a lack of sufficient knowledge in this field, the next part of the thesis focuses on a comparative study of the impact of different surface coatings on the magnetic imaging efficacy of SPIONs. The results indicate that the thickness of the silica coating and the presence of liposomal encapsulation around SPIONs play critical roles in determining their magnetic properties. The study suggests that there exists an optimal coating thickness that maximizes MPI and MRI performance, while excessive coating can lead to a decrease in sensitivity.
Overall, this thesis contributes to the advancement of SPION technology by addressing key challenges and demonstrating the feasibility of producing SPIONs with improved performance for biomedical imaging. The implications of this research are profound. The enhanced magnetic properties and imaging potential of the optimized SPIONs hold significant promise for the development of next-generation contrast agents, potentially leading to more accurate and sensitive diagnostic imaging. The findings also have broader applications, suggesting that the methodologies developed could be extended to other biomedically relevant nanomaterials, thereby impacting various aspects of nanomedicine, including targeted drug delivery, magnetic hyperthermia, and biosensing. The comprehensive body of work not only furthers our scientific understanding of SPIONs but also lays the groundwork for future innovations that could transform medical diagnostics and treatment strategies, ultimately enhancing patient outcomes.