Dual-Modal Magnetic Resonance and Fluorescence Imaging of Atherosclerotic Plaques in Vivo Using VCAM-1 Targeted Tobacco Mosaic Virus

Abstract

The underlying cause of major cardiovascular events, such as myocardial infarctions and strokes, is atherosclerosis. For accurate diagnosis of this inflammatory disease, molecular imaging is required. Toward this goal, we sought to develop a nanoparticle-based, high aspect ratio, molecularly targeted magnetic resonance MR imaging contrast agent. Specifically, we engineered the plant viral nanoparticle platform tobacco mosaic virus (TMV) to target vascular cell adhesion molecule (VCAM)-1, which is highly expressed on activated endothelial cells at atherosclerotic plaques. To achieve dual optical and MR imaging in an atherosclerotic ApoE−/− mouse model, TMV was modified to carry near-infrared dyes and chelated Gd ions. Our results indicate molecular targeting of atherosclerotic plaques. On the basis of the multivalency and multifunctionality, the targeted TMV-based MR probe increased the detection limit significantly; the injected dose of Gd ions could be further reduced by 3 orders of magnitude compared to the suggested clinical use, demonstrating the utility of targeted nanoparticle cargo delivery.

Paramagnetic Phospholipid-Based Micelles Targeting VCAM-1 Receptors for MRI Visualization of Inflammation

“…23, and 2.5 times higher than the r 1 value reported for nanosized agent based on the tobacco mosaic virus. 24 In the latter system, a number of ca. 1200 Gd-complexes per particle was estimated, which led to a particle relaxivity of 17520 s -1 mM -1 .…”

“…Moreover, MRI is often considered the technique of choice in the diagnosis of diseases with 5 (relaxivity of 14.6 s -1 mM Gd -1 at 1.5 T and 25°C). 24 Injected in a mouse model of atherosclerosis, this agent produced a two/threefold increase in MRI contrast when compared with both healthy mice and diseased animals administered with free Gd-DOTA.…”

Mesoporous silica nanoparticles functionalized with fluorescent and MRI reporters for the visualization of murine tumors overexpressing αvβ3receptors

“…For example, nanomaterials, such as dendrimers, 5 polymers, [6][7] proteins, 8 gold 9 and silica [10][11] nanoparticles have been applied as slowly moving carriers for Gd(III)-complexes. One of the most significant limitation of the currently reported nanosized T 1 -CAs is their large overall size (>100 nm) that markedly affect their in vivo distribution as they are quickly cleared by the reticuloendothelial system (RES).…”

Hyaluronic acid-decorated reconstituted high density lipoprotein targeting atherosclerotic lesions

“…Recently, researchers have discovered multiple potential targets preferentially presented on atherosclerotic progress, including some specific inflammatory cells and a number of particular cell surface receptors, etc. Several atherosclerotic lesions-targeted ligands have been developed hitherto, which contain phage display technology-derived special peptides targeting for vascular cellular adhesion molecule-1 (VCAM-1) [4], dextran sulfate for scavenge receptor type-A (SR-A) [5], phosphatidylserine for cluster of differentiation 36 (CD36) [6] and LyP-1 peptide for cell face p32 abundant in foam cell [7], etc. However, those atherosclerotic lesions-targeted ligands were almost exploited in atherosclerotic lesions imaging, but not involved in the lesions-targeted drug delivery for efficient treatment of atherosclerosis yet.…”