Dual-modal magnetic resonance and fluorescence imaging of atherosclerotic plaques in vivo using VCAM-1 targeted tobacco mosaic virus.
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 400x compared to the suggested clinical use, demonstrating the utility of targeted nanoparticle cargo delivery.
Department of Biomedical Engineering, ‡Department of Radiology, §Department of Materials Science and Engineering, and ∥Department of Macromolecular Engineering, Case Western Reserve University Schools of Medicine and Engineering , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
Michael A
MA
Bruckman
Kai
K
Jiang
Emily J
EJ
Simpson
Lauren N
LN
Randolph
Leonard G
LG
Luyt
Xin
X
Yu
Nicole F
NF
Steinmetz
D000818:Animals; D042783:Endothelial Cells / Q000000981:diagnostic imaging*; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000235:genetics; D011859:Radiography; D014027:Tobacco Mosaic Virus / Q000737:chemistry*; D019010:Vascular Cell Adhesion Molecule-1
D019010:Vascular Cell Adhesion Molecule-1