Ultrasmall Ferrite Nanoparticles Synthesized via Dynamic Simultaneous Thermal Decomposition for High-Performance and Multifunctional T₁ Magnetic Resonance Imaging Contrast Agent

Abstract

Large-scale synthesis of monodisperse ultrasmall metal ferrite nanoparticles as well as understanding the correlations between chemical composition and MR signal enhancement is critical for developing next-generation, ultrasensitive T magnetic resonance imaging (MRI) nanoprobes. Herein, taking ultrasmall MnFeO nanoparticles (UMFNPs) as a model system, we report a general dynamic simultaneous thermal decomposition (DSTD) strategy for controllable synthesis of monodisperse ultrasmall metal ferrite nanoparticles with sizes smaller than 4 nm. The comparison study revealed that the DSTD using the iron-eruciate paired with a metal-oleate precursor enabled a nucleation-doping process, which is crucial for particle size and distribution control of ultrasmall metal ferrite nanoparticles. The principle of DSTD synthesis has been further confirmed by synthesizing NiFeO and CoFeO nanoparticles with well-controlled sizes of ∼3 nm. More significantly, the success in DSTD synthesis allows us to tune both MR and biochemical properties of magnetic iron oxide nanoprobes by adjusting their chemical composition. Beneficial from the Mn dopant, the synthesized UMFNPs exhibited the highest r relaxivity (up to 8.43 mM s) among the ferrite nanoparticles with similar sizes reported so far and demonstrated a multifunctional T MR nanoprobe for in vivo high-resolution blood pool and liver-specific MRI simultaneously. Our study provides a general strategy to synthesize ultrasmall multicomponent magnetic nanoparticles, which offers possibilities for the chemical design of a highly sensitive ultrasmall magnetic nanoparticle based T MRI probe for various clinical diagnosis applications.

Manganese ferrite nanocubes as an MRI contrast agent

“…It is clear that NCs are highly crystalline and the observed diffraction peaks correspond to (111), (220), (311), (400), (422), (511), (440) planes, of the face-centred cubic spinel manganese-ferrite phase (ICDD card no. 10-0319) [20,21]. Besides, no impurities or secondary phases were observed which confirms the formation of pure phase MnFe NCs.…”

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

“…Fe 3+ has 5 unpaired electrons ( J = 5/2, S = 5/2, L = 0), the same as Mn 2+ , making Fe 3+ a promising candidate for T 1 CAs. 136,141-143 Small-sized iron oxide NPs show enhanced T 1 contrast effects due to the existence of a large number of Fe 3+ ions on the surface, suppressing T 2 relaxation by their small magnetic moment. The magnetic properties and r 1 values of various small-sized iron oxide NPs from 1.5 to 12 nm have been investigated (Fig.…”

“…also indicated similar size-dependences of r 1 values based on ultra-small MnFe 2 O 4 NPs. 136 Recently, exceedingly small iron oxide NPs with a hydrodynamic size of 4.7 nm, consisting of approximately 3 nm inorganic cores and about 1 nm organic hydrophilic shell, were reported to have high T 1 relaxivity ( r 1 = 5.2 mM −1 s −1 at 1.5 T). 142 Excreted mostly within the first 2.5 h through the urine, the exceedingly small iron oxide NPs have been successfully applied for high-performance magnetic resonance angiography (MRA) imaging (Fig.…”

Magnetic Nanomaterials for Advanced Regenerative Medicine: The Promise and Challenges

“…The inner‐sphere proton relaxation causes the direct coordination of water molecules by paramagnetic ions, while the outer‐sphere relaxation is affected by the dynamics and diffusion of nearby water molecules beyond those that are directly bonded. The relaxivity is the sum of inner‐ and outer‐sphere contributions, in which the relaxivity is the square ratio of the magnetization value. For an MION, the outer‐sphere contribution usually dominate the apparent relaxivity and tends to show an MR T 2 enhanced contrast .…”