Synthesis Of Magnetic Iron Oxide Nanoparticles And Their Applications In Magnetic Resonance Imaging

We adopted one-pot reaction to synthesize superparamagnetic iron oxide nanoparticles(SPIONs), in which the ferric triaetylacetonate (Fe(acac)3) was used as iron resource. X-raydiffraction (XRD) was used to determine crystalline phase of SPIONs. The particle size andshape of iron oxide were determined by transmission electron microscopy (TEM). Thehydrodynamic diameter and zeta potential of the SPIONs were determined by nano-particleand zeta potential Analyzer. The modification of the nanoparticles was recognized usingfourier transform infrared spectroscopy (FTIR). The magnetic properties of the resultantsamples were characterized by a superconducting quantum interference device (SQUID). Theiron concentration was measured by inductively coupled plasma atomic emissionspectrometer. Magnetic resonance (MR) relaxivities and T2*-weight MR images weremeasured by using a7.0T Bruker Biospec70/30USR nuclear magnetic resonancespectrometer. The key points are as follows:(1) We successfully synthesized SPIONs by thermal decomposition of the iron(III)acetylacetonate (Fe(acac)3) in poly(ethylene glycol)(PEG) as high-boiling point solvent,reducing agent and modifying agent. We discussed the growth mechanism of the magnetitenanoparticles. The results showed that the SPIONs we prepared were equiaxial crystal withuniform distribution. The particles size was about8.9nm and they had negative surface. TheM-H curves showed that the PEG coated SPIONs (PEG-SPIONs) have superparamagneticproperty and their saturation magnetization was53emu/g, in vivo T2*-weighted magneticresonance imaging (MRI) of the Kunming (KM) mouse brain after intravenous injection ofthe SPIONs showed good contrast effects, especially at5、10and30minutes.(2) SPIONs were synthesized by thermal decomposition of the iron(III) acetylacetonate(Fe(acac)3) in PEG containing poly(ethylene imine)(PEI) as modifying agents, and weresearched the influence of different molecular weight, different amount of PEI and differentreaction temperatures to the properties of the SPIONs, the results showed the differentmolecular weight of PEI, the amount of PEI and the reaction temperatures are all havesignificant effects on the shape evolution and size distribution of the SPIONs. The size ofSPIONs would be increased with the increase of molecular weight of PEI or the amount ofPEI at the same reaction temperatures, the average size of the SPIONs was in the range of5.2±1.0nm-13.7±2.3nm when the reaction temperatures increased from180oC to300oCwith0.3g PEI. FTIR spectroscopic results indicate that PEG and PEI are jointly attached to the surface of SPIONs. The PEG/PEI coated SPIONs (PEG/PEI-SPIONs) synthesized at260oC are not only highly soluble in deionized water hydrodynamic size and show longer timedispersion in water (for more than90days) but also soluble in many physiological bufferswith small hydrodynamic size and show excellent colloidal stability. The PEG/PEI-SPIONsshowed superparamagnetic behavior at room temperature with high saturation magnetization.The as-synthesized SPIONs exhibited high r2/r1ratios, and in vivo MRI of the mouse brainafter intravenous injection of the SPIONs showed good contrast effects.(3) We further conjugated transferrin (Tf) to PEG/PEI-SPIONs. The coupling reactionbetween particles and Tf was investigated via the dynamic light scattering (DLS) method bymonitoring the variation in the hydrodynamic size and zeta potential of the nanoparticlesbefore and after the conjugation reaction. The results showed that hydrodynamic diameter ofiron oxide nanoparticles increased from21to27nm and zeta potentials reduced from35to26mV after the conjugation reaction. The concentration of Tf in the resultant conjugate wasquantified by the Bradford method, it turned out that the concentration of Tf conjugate to theSPIONs surface was0.11mg/ml. T2*image of PEG/PEI-SPIONs connected Tf exhibits astronger contrast-enhanced imaging effect than the PEG-SPIONs、PEG/PEI-SPIONs, ThePEG/PEI-SPIONs connected Tf show stronger effects in reducing the T2*value incomparison with the mother PEG-SPIONs and PEG/PEI-SPIONs.