Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems

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 valida...

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Bibliographic Details
Published in:Polymer Chemistry
Main Authors: 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.
Other Authors: 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
Format: Article in Journal/Newspaper
Language:unknown
Published: Royal Society of Chemistry (RSC) 2020
Subjects:
Orca
Online Access:https://hdl.handle.net/1721.1/126188
Description
Summary: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. National Cancer Institute (Grant P30-CA14051)

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