Many captivating architectures incorporating magnetic nanoparticles have been designed for advanced medical and biological applications. Mostly, they aim at promising fields like the magnetically guided drug delivery; contrast improvement and visualization of labeled structures in sensitive imaging methods, e.g., magnetic resonance imaging (MRI) and magnetic particle imaging (MPI); magnetic fluid hyperthermia and heat-triggered drug release; and magnetically assisted separation in diagnostics. Among them, research focused on the development of magnetic nanoparticles as contrast agents for the non-invasive and non-ionizing MRI present an important example. The efficacy of a contrast agent is quantified by relaxivity, and explaining its dependence on various both extrinsic and intrinsic factors is still a matter of active research.
Although a plethora of multifunctional nanocomposite structures with miscellaneous coatings have been reported, the accurate description of such complex systems with respect to their behavior is often unfeasible. Here, a well-defined system of magnetic nanoparticles coated with amorphous silica is adopted to study the transverse relaxivity in connection to the theoretical models. A purely inorganic and chemically stable silica coating with a covalent structure offers an outstanding platform for model studies and provides colloidal stability of the particles in aqueous suspensions. Nonetheless, an unusual core magnetic material in a blocked state at room temperature, unprecedented in medical applications, is examined here - the gallium-doped epsilon polymorph of iron(III) oxide.
The ε-Fe2O3 is one of the five polymorphs of iron(III) oxide which are stable at ambient conditions, though the most intriguing one. Due to its large magnetocrystalline anisotropy, ε-Fe2O3 is distinguished by the giant coercive field of 2.1 T at room temperature. In ε-Fe2O3, the Fe3+ ions occupy four crystallographically inequivalent cation sites (three octahedral, one tetrahedral), which form four magnetic sublattices at room temperature. The moment in the tetrahedral site is lowered compared to the moments at octahedral sites, leading to a collinear ferrimagnetic structure.
However, upon cooling, a two-step spin-reorientation transition occurs between 150 K and 80 K, which is manifested by a rapid decrease of magnetization and coercive field.
The extraordinary magnetic properties of the epsilon polymorph can be modified by suitable substitution of Fe3+, under the condition that the stability of the phase is not violated by the dopant. Substituting diamagnetic metal cations for Fe3+ in tetrahedral sites can enhance the magnetization of the ferrimagnetic material. From the viewpoint of medical and biological applications, the doping with Ga3+, which has tetrahedral preference, poses a safe and effective choice due to its negligible toxicity.
In this study, magnetic nanoparticles of ε-Fe1.76Ga0.24O3 were prepared by thermal treatment of a mesoporous silica matrix impregnated with nitrates. The chosen Ga-doping enhanced magnetization and suppressed the low-temperature spin-reorientation transition typical for ε-Fe2O3. Despite the small mean size of 11 nm, the nanoparticles were in the blocked state over the whole temperature range under study, unlike standard superparamagnetic contrast agents based on other iron oxides or ferrites. The role of Ga-doping in local magnetic properties, e.g., the weakening of superexchange interactions due to the magnetic dilution effect, was demonstrated by 57Fe Mössbauer spectroscopy. The particles were further coated with silica and their performance in MRI was tested both in relaxometry and ultra-high-field imaging. Importantly, the obtained values of relaxivity are higher than reported for the undoped compound, which can be ascribed mainly to the higher magnetization, and are comparable to the relaxivities of traditional contrast agents approved for use in clinical practice. Due to the particle size distribution, the observed monotonous decrease of relaxivity with increasing temperature was interpreted in accordance with theoretical models by a combination of two regimes of 1H spin relaxation – motional averaging, which is valid for smaller particles and lower overall magnetization, and static dephasing for larger particles with larger magnetization. Although the static dephasing regime gained higher importance at 11.75 T and with a lower thickness of the coating, the motional averaging regime dominated in general and prevailed at higher temperatures due to faster water diffusion. The T2-contrast enhancement in MRI of the studied samples - related to the acceleration of the transverse relaxation - was comparable to ferucarbotran (Resovist).
