Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging

Molly A. Sowers, Jessica R. Mccombs, Ying Wang, Joseph T. Paletta, Stephen W. Morton, Erik C. Dreaden, Michael D. Boska, M. Francesca Ottaviani, Paula T. Hammond, Andrzej Rajca, Jeremiah A. Johnson

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents - ORCAFluors - for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ascorbate or ascorbate/glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging.

Original languageEnglish (US)
Article number5460
JournalNature communications
Volume5
DOIs
StatePublished - 2014

Fingerprint

Optical Imaging
Magnetic resonance
Oxidation-Reduction
magnetic resonance
Polymers
Fluorescence
Magnetic Resonance Imaging
Imaging techniques
fluorescence
Contrast Media
polymers
Molecular Imaging
Nanostructures
Heavy Metals
Molecular imaging
glutathione
Glutathione
Magnetic Resonance Spectroscopy
heavy metals
Relaxation time

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Sowers, M. A., Mccombs, J. R., Wang, Y., Paletta, J. T., Morton, S. W., Dreaden, E. C., ... Johnson, J. A. (2014). Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging. Nature communications, 5, [5460]. https://doi.org/10.1038/ncomms6460

Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging. / Sowers, Molly A.; Mccombs, Jessica R.; Wang, Ying; Paletta, Joseph T.; Morton, Stephen W.; Dreaden, Erik C.; Boska, Michael D.; Francesca Ottaviani, M.; Hammond, Paula T.; Rajca, Andrzej; Johnson, Jeremiah A.

In: Nature communications, Vol. 5, 5460, 2014.

Research output: Contribution to journalArticle

Sowers, MA, Mccombs, JR, Wang, Y, Paletta, JT, Morton, SW, Dreaden, EC, Boska, MD, Francesca Ottaviani, M, Hammond, PT, Rajca, A & Johnson, JA 2014, 'Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging', Nature communications, vol. 5, 5460. https://doi.org/10.1038/ncomms6460
Sowers, Molly A. ; Mccombs, Jessica R. ; Wang, Ying ; Paletta, Joseph T. ; Morton, Stephen W. ; Dreaden, Erik C. ; Boska, Michael D. ; Francesca Ottaviani, M. ; Hammond, Paula T. ; Rajca, Andrzej ; Johnson, Jeremiah A. / Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging. In: Nature communications. 2014 ; Vol. 5.
@article{5d7bbac4f78a4f5b9ba42cdd692a9171,
title = "Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging",
abstract = "Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents - ORCAFluors - for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ascorbate or ascorbate/glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging.",
author = "Sowers, {Molly A.} and Mccombs, {Jessica R.} and Ying Wang and Paletta, {Joseph T.} and Morton, {Stephen W.} and Dreaden, {Erik C.} and Boska, {Michael D.} and {Francesca Ottaviani}, M. and Hammond, {Paula T.} and Andrzej Rajca and Johnson, {Jeremiah A.}",
year = "2014",
doi = "10.1038/ncomms6460",
language = "English (US)",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging

AU - Sowers, Molly A.

AU - Mccombs, Jessica R.

AU - Wang, Ying

AU - Paletta, Joseph T.

AU - Morton, Stephen W.

AU - Dreaden, Erik C.

AU - Boska, Michael D.

AU - Francesca Ottaviani, M.

AU - Hammond, Paula T.

AU - Rajca, Andrzej

AU - Johnson, Jeremiah A.

PY - 2014

Y1 - 2014

N2 - Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents - ORCAFluors - for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ascorbate or ascorbate/glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging.

AB - Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents - ORCAFluors - for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ascorbate or ascorbate/glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging.

UR - http://www.scopus.com/inward/record.url?scp=84923338789&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923338789&partnerID=8YFLogxK

U2 - 10.1038/ncomms6460

DO - 10.1038/ncomms6460

M3 - Article

C2 - 25403521

AN - SCOPUS:84923338789

VL - 5

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 5460

ER -