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

Hung V.T. Nguyen, Alexandre Detappe, Peter Harvey, Nolan Gallagher, Clelia Mathieu, Michael P. Agius, Oksana Zavidij, Wencong Wang, Yivan Jiang, Andrzej Rajca, Alan Jasanoff, Irene M. Ghobrial, P. Peter Ghoroghchian, Jeremiah A. Johnson

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4768-4779
Number of pages12
JournalPolymer Chemistry
Volume11
Issue number29
DOIs
StatePublished - Aug 7 2020

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Polymers and Plastics
  • Organic Chemistry

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