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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ftpubmed:oai:pubmedcentral.nih.gov:6078806 2023-05-15T17:53:52+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. 2018-05-29 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078806/ http://www.ncbi.nlm.nih.gov/pubmed/29771534 https://doi.org/10.1021/acs.molpharmaceut.8b00262 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078806/ http://www.ncbi.nlm.nih.gov/pubmed/29771534 http://dx.doi.org/10.1021/acs.molpharmaceut.8b00262 Article Text 2018 ftpubmed https://doi.org/10.1021/acs.molpharmaceut.8b00262 2019-08-18T00:09:22Z 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 in vivoto 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(1) contrast at low field (<3.0 T), and T(2) 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. 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. Text Orca PubMed Central (PMC) Molecular Pharmaceutics 15 8 2973 2983 |
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Article 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 |
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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 in vivoto 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(1) contrast at low field (<3.0 T), and T(2) 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. 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. |
format |
Text |
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. |
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 |
publishDate |
2018 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078806/ http://www.ncbi.nlm.nih.gov/pubmed/29771534 https://doi.org/10.1021/acs.molpharmaceut.8b00262 |
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Orca |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078806/ http://www.ncbi.nlm.nih.gov/pubmed/29771534 http://dx.doi.org/10.1021/acs.molpharmaceut.8b00262 |
op_doi |
https://doi.org/10.1021/acs.molpharmaceut.8b00262 |
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Molecular Pharmaceutics |
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15 |
container_issue |
8 |
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2973 |
op_container_end_page |
2983 |
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1766161566220156928 |