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Biomimetic Modification And In Vivo Safety Assessment Of Superparamagnetic Iron Oxide Nanoparticles

Xinfeng Song, Xiangling Gu, Hanwen Sun, Chunhua Fu, Yancong Zhang, Pingxuan Dong

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The efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) for biomedical applications depends on the magnetic properties, long time stability in biological fluids, and specific targeting capacity. The properties of SPIONs were generally improved by surface modification, but common modification technologies were usually conducted with multi-steps under rigid conditions. In this work, a facile and simple approach to synthesize functionalized SPIONs contrast agents was set up. First of all, SPIONs were prepared by an improved ultrasonic co-precipitation method. Then the surfaces of these SPIONs were modified biomimeticly by dopamine (DA) with strong adhesion. At last, the c(RGDyK), a biomolecule with the capacity of specific targeting capacity towards liver tumor cells, were coupled with DA on SPIONs via Mannich reaction. Thus the novel magnetic composite nanoparticles (abbreviated as c(RGDyK)-PDA-SPIONs) were successfully prepared. The as-synthesized nanoparticles were characterized by scanning electron microscope (SEM), dynamic light scattering, magnetic hysteresis loop measuring instrument. As a result, that the c(RGDyK)- PDA-SPIONs had an average size of about 50 nm and uniform distribution, and had superparamagnetic properties, good water dispersion stability. The acute toxicity test of the as-synthesized c(RGDyK)-PDA-SPIONs to mice was also investigated. It was observed that LD50 of c(RGDyK)- PDA-SPIONs was 4.38 g/kg, with a 95% confidence interval ranging from 3.49 g/kg to 5.87 g/kg. These results indicated the novel c(RGDyK)-PDA-SPIONs had excellent biocompatibility, which was endowed with a potential capacity to serve as MRI contrast agents in diagnosis and treatment of the liver tumor.