Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor
Superoxide overproduction is known to occur in multiple disease states requiring critical care yet non-invasive 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...
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cracsoc:10.26434/chemrxiv.6241913 2023-07-30T04:06:10+02:00 Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor Dharmarwardana, Madushani Martins, André F. Chen, Zhuo Palacios, Philip M. Nowak, Chance M. Welch, Raymond P. Li, Shaobo Luzuriaga, Michael A. Bleris, Leonidas Pierce, Brad S. Sherry, A. Dean Gassensmith, Jeremiah J. 2018 http://dx.doi.org/10.26434/chemrxiv.6241913 https://ndownloader.figshare.com/files/11406758 unknown American Chemical Society (ACS) https://creativecommons.org/licenses/by-nc/4.0/ posted-content 2018 cracsoc https://doi.org/10.26434/chemrxiv.6241913 2023-07-17T00:15:55Z Superoxide overproduction is known to occur in multiple disease states requiring critical care yet non-invasive 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 <i>in vivo</i> 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 <i>T<sub>1</sub></i> contrast at low field (<3.0 T), and <i>T<sub>2</sub></i> contrast at high field (9.4 T). Additionally, we demonstrated that the unique topology of TMV allows for “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. <a>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.</a> Other/Unknown Material Orca ACS Publications (via Crossref) |
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ACS Publications (via Crossref) |
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Superoxide overproduction is known to occur in multiple disease states requiring critical care yet non-invasive 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 <i>in vivo</i> 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 <i>T<sub>1</sub></i> contrast at low field (<3.0 T), and <i>T<sub>2</sub></i> contrast at high field (9.4 T). Additionally, we demonstrated that the unique topology of TMV allows for “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. <a>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.</a> |
format |
Other/Unknown Material |
author |
Dharmarwardana, Madushani Martins, André F. Chen, Zhuo Palacios, Philip M. Nowak, Chance M. Welch, Raymond P. Li, Shaobo Luzuriaga, Michael A. Bleris, Leonidas Pierce, Brad S. Sherry, A. Dean Gassensmith, Jeremiah J. |
spellingShingle |
Dharmarwardana, Madushani Martins, André F. Chen, Zhuo Palacios, Philip M. Nowak, Chance M. Welch, Raymond P. Li, Shaobo Luzuriaga, Michael A. Bleris, Leonidas Pierce, Brad S. Sherry, A. Dean Gassensmith, Jeremiah J. Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor |
author_facet |
Dharmarwardana, Madushani Martins, André F. Chen, Zhuo Palacios, Philip M. Nowak, Chance M. Welch, Raymond P. Li, Shaobo Luzuriaga, Michael A. Bleris, Leonidas Pierce, Brad S. Sherry, A. Dean Gassensmith, Jeremiah J. |
author_sort |
Dharmarwardana, Madushani |
title |
Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor |
title_short |
Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor |
title_full |
Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor |
title_fullStr |
Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor |
title_full_unstemmed |
Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor |
title_sort |
nitroxyl modified tobacco mosaic virus as a metal-free high-relaxivity mri and epr active superoxide sensor |
publisher |
American Chemical Society (ACS) |
publishDate |
2018 |
url |
http://dx.doi.org/10.26434/chemrxiv.6241913 https://ndownloader.figshare.com/files/11406758 |
genre |
Orca |
genre_facet |
Orca |
op_rights |
https://creativecommons.org/licenses/by-nc/4.0/ |
op_doi |
https://doi.org/10.26434/chemrxiv.6241913 |
_version_ |
1772818620021211136 |