Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems
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Author(s)
Nguyen, Hung VanThanh
Detappe, Alexandre
Harvey, Peter
Gallagher, Nolan
Mathieu, Clelia
Agius, Michael P.
Zavidij, Oksana
Wang, Wencong
Jiang, Yivan
Rajca, Andrzej
Date Issued
June 2020
Journal
Polymer Chemistry
Publisher
Royal Society of Chemistry (RSC)
Citation
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
Version
Final published version
Abstract
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.
MIT Department
Massachusetts 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
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1039/d0py00558d
