Cyclic RGD functionalized liposomes targeted to activated platelets for thrombosis dual-mode magnetic resonance imaging

Abstract

Thrombotic disease is a serious threat to human health. The rapid and accurate detection of thrombosis is still a clinical challenge. To achieve the accurate diagnosis of thrombosis with magnetic resonance imaging (MRI), nanomaterials-based contrast agents have been developed in recent years. In this study, cyclic RGD functionalized liposomes targeted to the activated platelets are developed for thrombosis dual-mode MRI. The cyclic RGD functionalized liposomes (cRGD@MLP-Gd) encapsulated with gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and superparamagnetic iron oxide (SPIO) are prepared, and their thrombus-targeted T₁ and T₂ MRI potential is evaluated in vitro and in vivo. Results show that cRGD@MLP-Gd could actively bind to the activated platelets and gradually accumulate at the thrombus site with a T₁ − T₂ contrast enhancement imaging effect in vitro. In in vivo MRI experiments, cRGD@MLP-Gd exhibits a T₂ contrast enhancement at 1 h after intravenous administration, followed by a visibly larger T₁ contrast enhancement at the thrombus site. This dynamic property showed that cRGD@MLP-Gd could actively bind to thrombus and possessed an enhanced T₁ and T₂ dual-mode MRI effect in vivo. Our results establish the characterization, feasibility and superiority of cRGD@MLP-Gd for the rapid identification of thrombosis, showing great potential to improve diagnostic accuracy and sensitivity to thrombosis of the MRI technique.