Preparation of novel polyglycerol-iron oxide hybrid nanoparticles as high efficient MRI contrast agent for liver and kidney imaging

Introduction: Contrast agents are indispensable in magnetic resonance imaging (MRI), improving its sensitivity and specificity. Superparamagnetic Fe3O4 nanoparticles (MNPs) are suitable as negative MRI contrast agents, since these MNPs can enhance the alteration of proton relaxation in the tissue microenvironment, and thus provide better MR imaging specifically in diagnosis of liver tumor and metastasis.
In order to use these MNPs in biological systems it is necessary to
disperse them in water to form magnetic fluids by using appropriate
coatings. Therefore, many approaches have been focused on the
encapsulation of MNPs with biocompatible materials.
Hyperbranched polyglycerol is water-soluble and taking the biocompatibility of polyether structures such as PEG into account, its
polyether backbone makes it an attractive polymer for biomedical applications. In the present study, polyglycerol was chemically grafted onto superparamagnetic iron oxide nanoparticles to prepare a novel
organic/inorganic hybrid nanoparticles. This hybrid nanosystem is a stable water-based ferrofluid which can be used as MRI contrast agent.
Experimental: For reaching water-based ferrofluid, polyglycerol was grafted on the
surface of MNPs to obtain a new hybrid nanosystem. Superparamagnetic magnetite nanoparticles were prepared by coprecipitation method in aqueous media, then the surface of nanoparticles were modified with 3-
aminopropyltriethoxysilane to introduce the reactive amine groups on the surface of nanoparticles. After that, polyglycerol was grafted on the surface of nanoparticles by ring-opening anionic polymerization of
glycidol using n-bulyllithium as initiator.
Results: TEM image shows that the MNPs core have an average diameter of 14nm and are well-dispersed in water. Magnetization
measurement show that PG-grafted nanoparticles have saturation
magnetization about 46.6 emu/g and are superparamagnetic. The mean hydrodynamic diameter of PG-grafted nanoparticles is 39
nm. TGA curves show that the total magnetite content of PG-grafted nanoparticles is about 20%. NMRD profile (approved the superparamagnetic behavior of PG-grafted
MNPs with crystal radius of 7.5 nm and Ms aof41.8 emu/g. r1 and r2 relaxivities and r2/r1 ratios at different magnetic fields show the high potential of PG-grafted MNPs as T2 contrast agent.
T2-weighted MRI studies showed that negative contrast enhancement
increased by increasing the nanoparticle concentration. In vivo MRI studies on live mouse showed that PG-grafted MNPs are accumulated rapidly after injection in liver and also kidneys within first 6 min and also
they excrete from kidneys over time, while there is no evident change in signal intensity of the liver.
Conclusion: Highly stable water-based ferrofluid was prepared by chemically grafting of polyglycerol on the surface of MNPs. The results show their high efficiency as T2 (negative) MRI contrast agent in comparison with commercially available compounds.