Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems
Author(s)Nguyen, Hung VanThanh; Detappe, Alexandre; Harvey, Peter; Gallagher, Nolan; Mathieu, Clelia; Agius, Michael P.; Zavidij, Oksana; Wang, Wencong; Jiang, Yivan; Rajca, Andrzej; Jasanoff, Alan Pradip; Ghobrial, Irene M.; Ghoroghchian, Paiman Peter; Johnson, Jeremiah A.; ... Show more Show less
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Nitroxide-based organic-radical contrast agents (ORCAs) are promising as safe next-generation magnetic resonance imaging (MRI) tools. Nevertheless, stimuli-responsive ORCAs that enable MRI monitoring of prodrug activation have not been reported; such systems could open new avenues for prodrug validation and image-guided drug delivery. Here, we introduce a novel “pro-ORCA” concept that addresses this challenge. By covalent conjugation of nitroxides and drug molecules (doxorubicin, DOX) to the same brush-arm star polymer (BASP) through chemically identical cleavable linkers, we demonstrate that pro-ORCA and prodrug activation, i.e., ORCA and DOX release, leads to significant changes in MRI contrast that correlate with cytotoxicity. This approach is shown to be general for a range of commonly used linker cleavage mechanisms (e.g., photolysis and hydrolysis) and release rates. Pro-ORCAs could find applications as research tools or clinically viable “reporter theranostics” for in vitro and in vivo MRI-correlated prodrug activation.
DepartmentMassachusetts Institute of Technology. Department of Chemistry; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Massachusetts Institute of Technology. Department of Nuclear Science and Engineering; Koch Institute for Integrative Cancer Research at MIT
Royal Society of Chemistry (RSC)
Nguyen, Hung V.-T. et al. "Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems." Forthcoming in Polymer Chemistry 2020 (June 2020) © 2020 The Royal Society of Chemistry
Final published version