Date of Award
Open Access Dissertation
Magnetic resonance imaging (MRI)-guided magnetic nanofluid hyperthermia (MNFH) using iron oxide based superparamagnetic nanoparticles (SPNPs) has recently attracted considerable attention as a treatment modality for cancer theranostics, because MRI-guided MNFH can allow for diagnosis, therapeutics, and prognosis simultaneously using the same administrated magnetic nanofluid agent. However, several primary limiting factors: (1) insufficient AC magnetic heating induction (specific loss power/intrinsic loss power, SLP/ILP) at the biologically safe and physically tolerable range of AC magnetic field (HAC,safe: fappl × Happl < 3.0 ~ 5.0×109 A·m-1·s-1), (2) low r2- relaxivity directly related to the low resolution of MR contrast imaging, and (3) clinically unacceptable in-vitro/in-vivo biocompatibility with poor cellular uptake and enhanced permeability and retention, are still kept SPNPs challenging for a highly efficient cancer theranostics agent in clinic.
In this dissertation, innovatively designed and developed AC and DC magnetic softness enhanced dual-doped (Ni,Zn)-γFe2O3 SPNPs with significantly enhanced ILP (~ 4.0 nH m2 kg-1) at the Happl∙fappl = 1.23 ×109 A m-1 s-1 and r2-relaxivity (r2 = 660.4 mM-1 s-1) are synthesized. The enhanced ILP, and r2-relaxivity of dual-doped (Ni0.6Zn0.4)-γFe2O3 SPNPs were primarily attributed to the distinctly enhanced AC magnetic softness directly related to the HAC absorption and fappl resonance efficiency, and the DC magnetic softness dominantly controlled by the occupation and spatial distribution of Ni2+ in Oh vacancy sites, and Zn2+ cations in Td sites of γ-Fe2O3, respectively. In addition, pseudo single domain colloidal (NiZn)-γFe2O3 SPNPs (NiZn-γFe2O3 PSD-SPNPs) were physically and theoretically designed at the HAC,safe to meet the requirement for clinical application. The NiZn-γFe2O3 PSD-SPNPs show high ILP (~ 6.3 nHm2kg-1) and r2-relaxivity (r2 = 396 mM-1s-1). The remarkably enhanced effective relaxation time constant and out-of-phase magnetic susceptibility of the PSD-SPNPs at the HAC,safe were revealed as the main physical reason for the significance. The biocompatibility evaluated by in-vitro and in-vivo studies demonstrated that (Ni,Zn)-γFe2O3 SPNPs can be a promising candidate for highly efficient cancer theranostics agent in future nanomedicine. Furthermore, the contribution of spatial homogeneity of SPNP nanofluids to the r2-relaxivity has been investigated in T2-weighted MRI. According to the experimentally and theoretically analyzed results, the spatial homogeneity of nanofluids critically affects the r2-relaxivity and accordingly the MR contrast effect due to its contribution to the changes of m(M) (Hc ≈ Hk) of SPNP nanofluids. It was demonstrated that magnetic energy competition and water accessibility models, as well as the combinational model depending on the degree of spatial homogeneity are critical to accurately interpret the effects of spatial homogeneity on the r2-relaxivity for T2-weighted MR imaging.
Wang, J.(2023). Magnetic Softness Tuned Superparamagnetic Nanoparticles for Highly Efficient Cancer Theranostics. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/7457