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 (T 2) 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 T 2 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.

Nanoparticles for Thrombus Diagnosis and Therapy: Emerging Trends in Thrombus-theranostics

“…The results of this study show that nanoplatforms can improve the identification of intracranial aneurysms and thrombus associated with them, which can aid in the treatment of these conditions (Fig. 2 ) 84 . In another study, Ta et al synthesized a dual contrast iron oxide nanoparticle (DCIONs) for magnetic resonance imaging using co-precipitation at high temperature.…”

Imaging of intracranial aneurysms in animals: a systematic review of modalities

“…With targeted MRI contrast agent, it is thus possible to visualize an excess of inflammatory cells, but whether the method is sensitive enough for other potential IA instability markers remains to be proven. In this respect, it is interesting to mention that Zhang et al [ 183 ] used a nanoplatform (zinc and iron oxide nanoparticles targeting the platelets) to target thrombus in the rabbit elastase IA model. Hemodynamic imaging …”

“…The emergence of molecular imaging could allow for the in vivo visualization of these changes in the IA wall. So far, molecular imaging using targeted MRI contrast agents allowed for the visualization of the inflammation-associated tissue marker, myeloperoxidase [ 101 , 138 ], macrophage infiltration using ferumoxytol [ 181 ], and thrombus using a nanoplatform targeting the platelets [ 183 ] in animal IA models. The development of other targeted MRI contrast agents would critically help to elucidate modifications in the vessel wall during IA development and prior to rupture.…”

“…[ 182 ] 2021 X Surgical Rabbits Saccular X X Zhang Y. [ 183 ] 2021 X Surgical Rabbits Saccular X X Fries F. [ 184 ] 2022 X Surgical Rabbits Saccular X Hufnagl C. [ 185 ] 2022 X Surgical Rabbits Saccular X Wanderer S. [ 186 ] 2022 X Surgical Rabbits Saccular X …”

Molecular nanoprobe for diagnosis of cardiovascular diseases

“…MR imaging shows the promise not only for AS diagnosis, but also for thrombus [74,75]. For example, Wang and co-workers designed an activated platelet-targeted NP (MFe 2 O 4 −ZnDPA) consisting of Zn 0.4 Co 0.6 Fe 2 O 4 @Zn 0.4 Mn 0.6 Fe 2 O 4 as contrast agents and Zn (II)-bis(dipicolylamine) as targeting agents for MR imaging of thrombus (Figure 3E) [76]. The rate of change in the T 2 signal increased with the increasing Fe concentration, confirming the MFe 2 O 4 −ZnDPA possessed excellent MR characteristic (Figure 3F).…”