Synthesis and characterization of Gd-DTPA/fucoidan/peptide complex nanoparticle and in vitro magnetic resonance imaging of inflamed endothelial cells

Abstract

P-selectin overexpressed on activated endothelial cells and platelets is a new target for treatment of cancers and cardiovascular diseases such as atherosclerosis and thrombosis. In this study, depolymerized low molecular weight fucoidan (LMWF8775) and a thermolysin-hydrolyzed prolamine peptide (TPP1880) were prepared. TPP1880 and LMWF8775 were able to form self-assembled complex nanoparticles (CNP5). The formation of TPP1880/LMWF8775 CNP5 was characterized by Fourier-transform infrared spectra, circular dichroism spectra and isothermal titration calorimetry. The CNP5 selectively targeted PMA-stimulated, inflamed endothelial cells (HUVECs) with high expression of P-selectin. Gd-DTPA MRI contrast agent was successfully loaded in the CNP5 with better T-1 relaxivity and selectively accumulated in the activated HUVECs with increased MRI intensity and reduced cytotoxicity as compared to free Gd-DTPA. Our results suggest that the TPP1880/LMWF8775 CNP5 may have potential in future for early diagnosis of cardiovascular diseases and cancers in which the endothelium is inflamed or activated.