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Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2018 Aug 06; Vol. 15 (8), pp. 2973-2983. Date of Electronic Publication: 2018 May 29. - Publication Year :
- 2018
-
Abstract
- Superoxide overproduction is known to occur in multiple disease states requiring critical care; yet, noninvasive detection of superoxide in deep tissue remains a challenge. Herein, we report a metal-free magnetic resonance imaging (MRI) and electron paramagnetic resonance (EPR) active contrast agent prepared by "click conjugating" paramagnetic organic radical contrast agents (ORCAs) to the surface of tobacco mosaic virus (TMV). While ORCAs are known to be reduced in vivo to an MRI/EPR silent state, their oxidation is facilitated specifically by reactive oxygen species-in particular, superoxide-and are largely unaffected by peroxides and molecular oxygen. Unfortunately, single molecule ORCAs typically offer weak MRI contrast. In contrast, our data confirm that the macromolecular ORCA-TMV conjugates show marked enhancement for T <subscript>1</subscript> contrast at low field (<3.0 T) and T <subscript>2</subscript> contrast at high field (9.4 T). Additionally, we demonstrated that the unique topology of TMV allows for a "quenchless fluorescent" bimodal probe for concurrent fluorescence and MRI/EPR imaging, which was made possible by exploiting the unique inner and outer surface of the TMV nanoparticle. Finally, we show TMV-ORCAs do not respond to normal cellular respiration, minimizing the likelihood for background, yet still respond to enzymatically produced superoxide in complicated biological fluids like serum.
- Subjects :
- Animals
Chemistry, Pharmaceutical
Click Chemistry
Electron Spin Resonance Spectroscopy methods
HeLa Cells
Humans
Magnetic Resonance Imaging methods
Mice
Microscopy, Confocal
Microscopy, Fluorescence
Molecular Imaging methods
Nanoconjugates chemistry
RAW 264.7 Cells
Contrast Media chemistry
Molecular Probes chemistry
Superoxides metabolism
Tobacco Mosaic Virus chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 15
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 29771534
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.8b00262