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

Abstract

Purpose 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.

Engineering molecular nanoprobes to target early atherosclerosis: Precise diagnostic tools and promising therapeutic carriers

“…In addition to overcoming the limitations of single-mode imaging, multi-mode imaging can achieve better imaging effects through combining the advantages of various imaging modalities, to realize the early diagnosis of atherosclerosis. Of note, those fabricated multimodal imaging nanoparticles with reactive oxygen species (ROS)-scavenging ability have been reported to provide a new avenue for the diagnosis and treatment of vulnerable plaques, constructing a novel theranostic nanoplatform for atherosclerosis 48 . Overall, recent advances in imaging and treatment of atherosclerosis based on various nanoprobes bring a couple of new opportunities in the future.…”

“…At last, Dai et al submitted that the ROS-scavenging nanoparticles can mediate MR/fluorescence dual-modality imaging tracing of vulnerable plaques. It is worth pointing out that this is the only study to especially address the therapeutic potential of dual-modality nanoprobes in atherosclerosis, mechanistically through the downergulation of inflammation, apoptosis, and foam cell formation 48 . Taken together, optical/MR dual-model imaging nanoprobes have been under active investigation, and have gradually shown promising potential in early diagnosis and prevention of atherosclerosis.…”

Design and Fabrication of Environmentally Responsive Nanoparticles for the Diagnosis and Treatment of Atherosclerosis

“…Fluorescent dyes or luminescent substances may be targeted with the assistance of nanocarriers, subsequently aggregating with the imaging lesion location. Natural fluorescent NPs, such as quantum dots, have been employed in AS imaging to provide characteristic information regarding plaque composition and progression …”

“…Natural fluorescent NPs, such as quantum dots, have been employed in AS imaging to provide characteristic information regarding plaque composition and progression. 38 (3) Personalized treatment of AS: Nanotechnology offers the potential for personalized treatment of AS by allowing the customization of NPs to target specific plaque components or patient-specific responses to treatment. 39 The properties of NPs, such as size, surface chemistry, and release kinetics, can be tailored to optimize their effectiveness in treating AS.…”

“…Fluorescent dyes or luminescent substances may be targeted with the assistance of nanocarriers, subsequently aggregating with the imaging lesion location. Natural fluorescent NPs, such as quantum dots, have been employed in AS imaging to provide characteristic information regarding plaque composition and progression Personalized treatment of AS: Nanotechnology offers the potential for personalized treatment of AS by allowing the customization of NPs to target specific plaque components or patient-specific responses to treatment .…”