Citric acid coated ultrasmall superparamagnetic iron oxide nanoparticles conjugated with lactoferrin for targeted negative MR imaging of glioma.

The proposed study was to develop the preparation of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) modified with citric acid, with surface conjugated with lactoferrin (Lf), which used as a potential targeted contrast agent for magnetic resonance imaging (MRI) of brain glioma. USPIONs were prepared by the thermal decomposition method. The hydrophobic USPIONs were coated with citric acid by the ligand exchange method. Then, Lf was conjugated into the surface of USPIONs. The obtained Lf-USPIONs were analyzed by fourier transform infrared (FTIR) spectroscopy and polyacrylamide gel electrophoresis. The size, size distribution, shape and superparamagnetic property of Lf-USPIONs were investigated with TEM and vibrating sample magnetometer (VSM). Both FTIR and electrophoresis analysis demonstrated the successful conjugation of Lf to the surface of USPIONs. The average size of Lf-USPIONs was about 8.4 ± 0.5 nm, which was determined using the statistics of measured over 100 nanoparticles in the TEM image, with a negative charge of -7.3 ± 0.2 mV. TEM imaging revealed that Lf-USPIONs were good in dispersion and polygonal in morphology. VSM results indicated that Lf-USPIONs were superparamagnetic and the saturated magnetic intensity was about 69.8 emu/g. The Lf-USPIONs also showed good biocompatibility in hemolysis, cytotoxicity, cell migration and blood biochemistry studies. MR imaging results in vitro and in vivo indicated that Lf-USPIONs exhibited good negative contrast enhancement. Taken together, Lf-USPIONs hold great potential for brain gliomas MR imaging as a nanosized targeted contrast agent.