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.Massachusetts Institute of Technology. Department of ChemistryMassachusetts Institute of Technology. Research Support CommitteeLincoln LaboratoryNational Institutes of Health (U.S.) (NIBIB 1R21EB018529-01A1)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F32EB017614-01)United States. Dept. of Defense. Ovarian Cancer Research Program (Teal Innovator Award)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051