Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging.
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.
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Molly A
MA
Sowers
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Jessica R
JR
McCombs
Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, USA.
Ying
Y
Wang
Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, USA.
Joseph T
JT
Paletta
Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Stephen W
SW
Morton
Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Erik C
EC
Dreaden
Department of Radiology, University of Nebraska Medical Center, Omaha, Nebraska 68198.
Michael D
MD
Boska
Department of Earth, Life and Environmental Sciences, University of Urbino, Loc. Corcicchia, 61029 Urbino, Italy.
M Francesca
MF
Ottaviani
Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Paula T
PT
Hammond
Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, USA.
Andrzej
A
Rajca
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Jeremiah A
JA
Johnson
D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D005260:Female; D005453:Fluorescence; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000295:instrumentation*; D009589:Nitrogen Oxides / Q000737:chemistry; D010084:Oxidation-Reduction; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
D003287:Contrast Media; D009589:Nitrogen Oxides; D011108:Polymers; C039900:nitroxyl; D001205:Ascorbic Acid