Activated Platelet-Homing Nanoplatform for Targeting Magnetic Resonance Imaging of Aneurysm-Related Thrombus in Rabbits.

Abstract

Thrombosis is closely related to the instability of intracranial aneurysm (IA), whose rupture is associated with high morbidity and mortality. It is difficult to detect an IA-related thrombus because traditional magnetic resonance imaging (MRI) and even contrast-enhanced MRI cannot clearly distinguish a thrombus from the surrounding tissues. Herein, a nanoplatform [(MFe2O4-ZnDPA nanoparticles (NPs)], consisting of Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4 NPs for imaging and Zn(II)-bis(dipicolylamine) (ZnDPA) for thrombus targeting, is constructed to target an experimental aneurysm-related thrombus in rabbits via MRI. In vitro experiments including platelet safety evaluation primarily prove that MFe2O4-ZnDPA NPs with a high MRI transverse relaxation time (T2) have good biocompatibility. MFe2O4-ZnDPA NPs could target a thrombus via the special interaction between ZnDPA and phosphatidylserine of activated platelets in the thrombus through MRI and Fe quantification assays. Moreover, after MFe2O4-ZnDPA NPs are injected into the ear vein of common carotid artery aneurysm model rabbits, MRI shows that MFe2O4-ZnDPA NPs could accumulate in the aneurysm-related thrombus from 0 to 15 min after injection and decrease in the next 45 min. Meanwhile, MFe2O4-ZnDPA NPs could decrease the MRI T2 signal of the aneurysm-related thrombus to enhance the outline of the aneurysm. This study demonstrates that a nanoplatform can enhance the detection of an aneurysm-related thrombus as well as aneurysm itself to assist further treatment of IA.