Targeted Therapy of Atherosclerosis Vulnerable Plaque by ROS-Scavenging Nanoparticles and MR/Fluorescence Dual-Modality Imaging Tracing

Abstract

Yue Dai,1,2,* Xuan Sha,1,* Xiaoxi Song,1 Xiuli Zhang,1,2 Mengyuan Xing,1 Siwen Liu,1 Kai Xu,1,2 Jingjing Li1,2 1School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kai Xu; Jingjing Li, Email [email protected]; [email protected]: Early diagnosis and treatment of atherosclerosis (AS) vulnerable plaque has important clinical significance for the prognosis of patients. In this work, the integrated diagnosis and treatment nanoparticles based on Gd-doped Prussian blue (GPB) were constructed for the fluorescence/MR dual-mode imaging and anti-ROS treatment of vulnerable AS plaques in vitro and in vivo.Methods: To fabricate the theranostic NPs, GPB was modified with water-soluble polymer polyethyleneimine (PEI), fluorescence molecule rhodamine (Rd), and targeted molecule dextran sulfate (DS) step by step via electrostatic adsorption to construct GPRD NPs. The fluorescence/MR imaging ability and various nano-enzymes activity of GPRD NPs were detected, and the biocompatibility and safety of GPRD were also evaluated. Subsequently, RAW264.7 cells and ApoE -/- model mice were used to evaluate the effect of GPRD NPs on the targeted dual-mode imaging and anti-ROS treatment of vulnerable plaque in vitro and in vivo.Results: The experimental results showed that our fabricated GPRD NPs not only displayed excellent MR/fluorescence dual-modality imaging of vulnerable plaque in vivo but also effectively utilized the nano-enzyme activity of GPB to inhibit the AS progress by ROS scavenging and the following reduction of inflammation, apoptosis, and foam cells’ formation, providing a new avenue for the diagnosis and treatment of AS vulnerable plaque.Conclusion: The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.Graphical Abstract: Keywords: vulnerable plaques, ROS scavengers, nano-enzyme, MRI, fluorescence imaging

Keywords

• vulnerable plaques
• ros scavengers
• nano-enzyme
• mri
• fluorescence imaging