Dextran Sulfate-Modified and pH-Responsive Nanoprobes for Magnetic Resonance/Fluorescence Dual-Modality Imaging of Vulnerable Plaques

Abstract

Triggered by the vulnerability to atherosclerotic plaques, cardiovascular diseases (CVDs) have become a main reason for high mortality worldwide. Thus, there is an urgent need to develop functional molecular imaging modalities to improve the detection rate of vulnerable plaques. In this study, polyethyleneimine (PEI) was coated on the surface of mesoporous silica nanoprobes (MSN) loaded with Gd₂O₃ (MSN@Gd₂O₃), followed by coupling the fluorescent dye carboxylated heptamethine cyanine (IR808), and then the dextran sulfate (DS) was modified on the surface of MSN@Gd₂O₃@IR808 by electrostatic adsorption, to construct a targeted and pH-responsive magnetic resonance (MR)/near-infrared fluorescence imaging (NIRF) dual-modal nanoprobe (MSN@Gd₂O₃@IR808@DS nanoparticles). The nanoprobe presented a more concentrated distribution of spherical shapes in transmission electron microscopy. In vitro simulated vulnerable plaque microenvironment (pH = 5.5) presented significant T₁-weighted imaging (T₁WI) signal and longitudinal relaxation in the nanoprobe. Immunofluorescence staining and cellular uptake assays showed that MSN@Gd₂O₃@IR808@DS nanoparticles have the ability to specially bind to scavenger receptors A (SR-A). In vascular endothelium from the high-fat diet (HFD) New Zealand White rabbits, MSN@Gd₂O₃@IR808@DS nanoparticles can exhibit specific contrast-enhanced signals by MR/NIRF dual-modal imaging. In addition, cytotoxicity assays and hematoxylin and eosin (H&E) staining results demonstrated that MSN@Gd₂O₃@IR808@DS nanoparticles have good biocompatibility. Hence, this multifunctional MR/NIRF bimodal nanoprobe provides new experimental and technological ideas for the accurate diagnosis of vulnerable plaques.