Silica functionalized ultra small iron oxide nanoparticles (10NPs) for T1-weighted magnetic resonance imaging (MRI) contrast agent

摘要

Magnetic resonance imaging (MRI), a sensitive and sophisticated promising three-dimensional tomographic noninvasive diagnostic technique, has intrinsic advantage in safety compared with optical imaging and radiotracer modalities. However, MRI inorganic contrast agents are less sensitive than complexes used in other imaging techniques. Usually clinical used Gd-based complexes MRI-T1 contrast agents are toxic. Therefore, demand for highly dispersive, non-toxic novel T1-weighted MRI potential candidate with ultrasensitive imaging and advanced functionality is very high. In this report, silica coated ultra small monodispersed super-paramagnetic iron oxide nanoparticles were synthesized via thermal decomposition of iron-oleate which demonstrated high performance T1-weighted MRI contrast agent for heart, liver, kidney and bladder based on in vivo imaging analyses. X-ray diffraction (XRD) and Raman spectroscopy analyses revealed the purity in phase of the prepared SPIONPs. Transmission electron microscopy (TEM) results have illustrated that the diameter of ultra small SPIONPs was in the range of 4nm and the average size of Fe304@SiO2 was about 30nm-40nm. These magnetite nanoparticles exhibited weak magnetic moment at room temperature because of spin-canting effect which escorted high positive signal enhancement ability. MCF-7 and HeLa cells viabilities experiments of demonstrated good biocompatibility of the SPIONPs. In addition, the silica coated ultra small (4nm-sized) magnetite nanoparticles exhibited a good r1 relaxivity of 1.2 and low r2/r1 ratio of 6.5, attributed to low magnetization, large surface area and 5 unpaired valence electrons on the surface of Fe3+. In vivo T1-weighted MR imaging of heart, liver, kidney and bladder in mice after intravenous injection of nanoparticles further verified the high sensitivity and biocompatibility of as-synthesized magnetite nanoparticles. The above mentioned results revealed silica coated ultra small SPIONPs as an excellent candidate for T1 contrast agent with extraordinary capability to enhance MR images. This project is financially supported by Zhejiang Provincial Natural Science Foundation of China (Grants no. BSH1401038), by China Postdoctoral Research program (Grant no. 2014M561799), by the National Natural Science Foundation o! China (U1432114), by the Hundred Talents Program of Chinese Academy of Sciences (2010-735), and by Key Breakthrough Program of Chinese Academy of Sciences (KGZD-EW-T06). The authors also thank Jiangjun Zheng and Bin Chen from Ningbo no. 2 Hospital for helping test the MRI data. The authors appreciate the cooperation of Ningbo University, Shanghai Niumag and Huantong companies for their time and help. Dr. M. Zubair Iqbal is thankful to Chinese Academy of Sciences and The world Academy of Science for awarding CAS-TWAS postdoctoral fellowship (2014FFGB0004)..