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.