Specific Targeting MRI of Chitosan Oligosaccharide Modified Fe3O4 Nanoprobe on Macrophage and the Inhibition of Macrophage Foaming Induced by ox-LDL

Abstract

Atherosclerosis (AS) is a primary cause of morbidity and mortality all over the world. Molecular imaging techniques can enable early localization and diagnosis of atherosclerosis plaques. Recent newly developed chitooligosaccharides (CSO) is considered to be capable of target mannose receptors on the surface of macrophages and to inhibit foam cell formation. Here we present a targeting magnetic resonance imaging (MRI) nanoprobe, which was successfully constructed with polyacrylic acid (PAA) modified nanometer iron oxide (Fe3O4) as the core, and coating with CSO molecules, possessing the abilities of targeted MRI and specifically inhibition of the formation of foamy macrophages in the atherosclerotic process. The experimental results showed that the distributions of PAA-Fe3O4 and CSO-PAA-Fe3O4 were uniform and the corresponding sizes were about 5.93 nm and 8.15 nm, respectively. The Fourier transform infrared spectra (FTIR) testified the CSO was coupled with PAA-Fe3O4 successfully. After coupled with CSO, the r1 of PAA-Fe3O4 was increased from 5.317 mM s-1 to 6.147 mM s-1, indicating their potential as MRI contrast agent. Oil Red O staining and total cholesterols (TC) determination showed that CSO-PAA-Fe3O4 could significantly inhibit the foaming process of RAW264.7 cells induced by oxidatively modified low density lipoprotein (ox-LDL). In vitro cellular MRI displayed that, compared with PAA-Fe3O4,CSO-PAA-Fe3O4 could lower the T1 relaxation time of RAW264.7 cells better. In summary, construction of CSO-PAA-Fe3O4 nanoprobe in this study could realize the targeted MRI of macrophages and inhibition of ox-LDL induced macrophage foaming process. This will provide a new avenue in the diagnosis and treatment of AS.