Early diagnosis of cerebral thrombosis by EGFP-EGF1 protein conjugated ferroferric oxide magnetic nanoparticles.

Abstract

Cerebral thrombosis disease is a worldwide problem, with high rates of morbidity, disability, and mortality. Magnetic resonance imaging diffusion-weighted imaging was used as an important early diagnostic method for cerebral thrombotic diseases; however, its diagnosis time is 2 h after onset. In this study, we designed EGFP-EGF1-NP-Fe3O4 for earlier diagnosis of cerebral thrombosis by taking advantage of EGFP-EGF1 fusion protein, in which EGF1 can bind with tissue factor and enhanced green fluorescent protein has previously been widely used as a fluorescent protein marker. EGFP-EGF1-NP-Fe3O4 or NP-Fe3O4 reaches the highest concentration in the infarction areas in 1 h. To evaluate the targeting ability of EGFP-EGF1-NP-Fe3O4, a fluorochrome dye, Dir, was loaded into the nanoparticle. As shown by the in vivo organ multispectral fluorescence imaging, Dir-loaded EGFP-EGF1-NP-Fe3O4 exhibited higher fluorescence than those of model rats treated with Dir-loaded NP-Fe3O4. Coronal frozen sections and transmission electron microscope further showed that EGFP-EGF1-NP-Fe3O4 was mainly accumulated in the tissue factor exposure region of brain. The data indicated that the EGFP-EGF1-NP-Fe3O4 targeted cerebral thrombosis and might be applied in the early diagnosis of intracranial thrombosis.